MMP2

Gene Summary

Gene:MMP2; matrix metallopeptidase 2
Aliases: CLG4, MONA, CLG4A, MMP-2, TBE-1, MMP-II
Location:16q12.2
Summary:This gene is a member of the matrix metalloproteinase (MMP) gene family, that are zinc-dependent enzymes capable of cleaving components of the extracellular matrix and molecules involved in signal transduction. The protein encoded by this gene is a gelatinase A, type IV collagenase, that contains three fibronectin type II repeats in its catalytic site that allow binding of denatured type IV and V collagen and elastin. Unlike most MMP family members, activation of this protein can occur on the cell membrane. This enzyme can be activated extracellularly by proteases, or, intracellulary by its S-glutathiolation with no requirement for proteolytical removal of the pro-domain. This protein is thought to be involved in multiple pathways including roles in the nervous system, endometrial menstrual breakdown, regulation of vascularization, and metastasis. Mutations in this gene have been associated with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis (NAO) syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]
Databases:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:72 kDa type IV collagenase
Source:NCBIAccessed: 11 March, 2017

Ontology:

What does this gene/protein do?
Show (24)
Pathways:What pathways are this gene/protein implicaed in?
Show (3)

Cancer Overview

Research Indicators

Publications Per Year (1992-2017)
Graph generated 11 March 2017 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 11 March, 2017 using data from PubMed, MeSH and CancerIndex

Latest Publications: MMP2 (cancer-related)

Dai L, Wang G, Pan W
Andrographolide Inhibits Proliferation and Metastasis of SGC7901 Gastric Cancer Cells.
Biomed Res Int. 2017; 2017:6242103 [PubMed] Free Access to Full Article Related Publications
To explore the mechanisms by which andrographolide inhibits gastric cancer cell proliferation and metastasis, we employed the gastric cell line SGC7901 to investigate the anticancer effects of andrographolide. The cell survival ratio, cell migration and invasion, cell cycle, apoptosis, and matrix metalloproteinase activity were assessed. Moreover, western blotting and real-time PCR were used to examine the protein expression levels and the mRNA expression levels, respectively. The survival ratio of cells decreased with an increasing concentration of andrographolide in a dose-dependent manner. Consistent results were also obtained using an apoptosis assay, as detected by flow cytometry. The cell cycle was blocked at the G2/M2 phase by andrographolide treatment, and the proportion of cells arrested at G1/M was enhanced as the dose increased. Similarly, wound healing and Transwell assays showed reduced migration and invasion of the gastric cancer cells at various concentrations of andrographolide. Andrographolide can inhibit cell proliferation, invasion, and migration, block the cell cycle, and promote apoptosis in SGC7901 cells. The mechanisms may include upregulated expression of Timp-1/2, cyclin B1, p-Cdc2, Bax, and Bik and downregulated expression of MMP-2/9 and antiapoptosis protein Bcl-2.

Yang J, Wang C, Zhang Z, et al.
Curcumin inhibits the survival and metastasis of prostate cancer cells via the Notch-1 signaling pathway.
APMIS. 2017; 125(2):134-140 [PubMed] Related Publications
Prostate cancer is one of the most common malignancies in men, and it urgently demands precise interventions that target the signaling pathways implicated in its initiation, progression, and metastasis. The Notch-1 signaling pathway is closely associated with the pathophysiology of prostate cancer. This study investigated the antitumor effects and mechanisms of curcumin, which is a well-known natural compound from curcuminoids, in prostate cancer cells. Viability, proliferation, and migration were analyzed in two prostate cancer cell lines, DU145 and PC3, after curcumin treatment. Whether the Notch-1 signaling pathway is involved in the antitumor effects of curcumin was examined. Curcumin inhibited the survival and proliferation of PC3 and DU145 cells in a dose- and time-dependent manner and inhibited DU145 migration. Curcumin did not affect the expression of Notch-1 or its active product NICD, but it did inhibit the expression of MT1-MMP and MMP2 proteins in DU145 cells. We found that curcumin inhibited the DNA-binding ability of NICD in DU145 cells. In conclusion, curcumin inhibited the survival and metastasis of prostate cancer cells via the Notch-1 signaling pathway.

Zhou Z, Li Y, Wang H, et al.
Biological Features of a Renal Cell Carcinoma Cell Line Derived from Spinal Metastasis.
DNA Cell Biol. 2017; 36(2):168-176 [PubMed] Related Publications
The establishment of a metastatic renal cell carcinoma (mRCC) cell line can facilitate the search for molecular mechanisms involved in RCC metastasis. A novel human mRCC cell line, designated RCC96, was established from an mRCC of the spine from a 65-year-old Chinese man. Morphology, cell cycle phase, chromosome number, cell capability of migration, tumorigenicity in nude mice, and cytogenetic features of RCC96 were investigated. Cell growth curve was detected and the cell number doubling time was 52 h. Karyotype analysis showed that these cells were polyploidy. Transmission electron microscope showed that cells were with large atypical nuclei, well-developed rough endoplasmic reticulum, rich Golgi complex, and mitochondria, as well as visible microacinar in the cytoplasm. PCR and immunofluorescence staining demonstrated that the expression of some genes such as KISS-1, MMP2, and VEGF in RCC96 was not entirely consistent with that in other RCC cell lines, indicating the differences between primary and metastatic RCC cell lines. The RCC96 cell line may serve as a useful tool for studying the molecular pathogenesis and testing new therapeutic reagents for mRCC.

Liu YF, Liu QQ, Zhang YH, Qiu JH
Annexin A3 Knockdown Suppresses Lung Adenocarcinoma.
Anal Cell Pathol (Amst). 2016; 2016:4131403 [PubMed] Free Access to Full Article Related Publications
Our previous study identified an elevated abundance of annexin A3 (Anxa3) as a novel prognostic biomarker of lung adenocarcinoma (LADC) through quantitative proteomics analysis. However, the biological functions of Anxa3 in LADC are not fully clear. In this study, in vitro and in vivo assays were performed to investigate the effects of Anxa3 downregulation on the growth, migration, invasion, metastasis, and signaling pathway activation of LADC cells. After Anxa3 downregulation, the growth of A549 and LTEP-a2 LADC cells was slowed and they showed decreased migration and invasion in vitro. Anxa3 knockdown significantly inhibited tumor formation by A549 cells in vivo; while many metastases were formed by control A549 cells, there were obvious reductions in the numbers of lung, liver, and brain metastases formed by Anxa3 knockdown in A549 cells. Furthermore, Anxa3 knockdown significantly decreased MMP-2 and N-cadherin expression and increased E-cadherin expression both in cell lines in vitro and in tumor nodules examined during in vivo tumorigenesis assays. Interestingly, Anxa3 downregulation reduced the phosphorylated levels of MEK and ERK. In summary, Anxa3 knockdown inhibited the growth, migration, invasion, and metastasis of LADC, decreased the activation of the MEK/ERK signaling pathway, and modulated the expression of MMP-2, E-cadherin, and N-cadherin.

Kim NI, Kim GE, Lee JS, Park MH
In phyllodes tumors of the breast expression of SPARC (osteonectin/BM40) mRNA by in situ hybridization correlates with protein expression by immunohistochemistry and is associated with tumor progression.
Virchows Arch. 2017; 470(1):91-98 [PubMed] Related Publications
Secreted protein acidic and rich in cysteine (SPARC) plays an essential role in tumor invasion and metastasis. The present work was undertaken to detect expression of SPARC mRNA in phyllodes tumors (PTs) and its association with SPARC protein expression. This study also evaluated expression of SPARC mRNA and its correlation between grade and clinical behavior of PTs. In addition, we assessed in PTs the association of expression of SPARC with that of matrix metalloproteinase (MMP)-2 and of MMP-9. SPARC mRNA expression was determined by RNAscope in situ hybridization (ISH) in 50 benign, 22 borderline, and 10 malignant PTs using a tissue microarray. Furthermore, we applied immunohistochemistry (IHC) to examine expression of SPARC, MMP-2, and MMP-9. SPARC mRNA appeared to be concentrated mainly in the stromal compartment of PTs. IHC staining patterns of SPARC protein showed concordance with SPARC mRNA ISH results. Stromal SPARC expression increased continuously as PTs progress from benign through borderline to malignant PTs, both at mRNA (using ISH) (P = 0.044) and protein level (using IHC) (P = 0.000). The recurrence percentage was higher in the stromal SPARC mRNA or protein-positive group than in the SPARC-negative group but this difference was not statistically significant. Stromal SPARC mRNA and protein expression was associated with PT grade and correlated with MMP-2 expression. These results indicate that SPARC-mediated degradation of the extracellular matrix, and its possible association with MMPs, might contribute to progression of PTs.

Wang D, Wang D, Wang N, et al.
Long Non-Coding RNA BANCR Promotes Endometrial Cancer Cell Proliferation and Invasion by Regulating MMP2 and MMP1 via ERK/MAPK Signaling Pathway.
Cell Physiol Biochem. 2016; 40(3-4):644-656 [PubMed] Related Publications
BACKGROUND/AIMS: Microarray screening had found BRAF-activated non-coding RNA (BANCR) was significantly upregulated in type 1 endometrial cancer (EC). This study aimed to assess the potential role of long non-coding RNA (lncRNA) BANCR in the pathogenesis and progression of type 1 EC.
METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to confirm the expression of BANCR in type 1 EC tissue, and analyze its clinical significance. In vitro, RNA interference (siRNA) was used to investigate the biological role of BANCR in type 1 EC.
RESULTS: qRT-PCR revealed that the expression of lncRNA BANCR was higher in type 1 EC (P<0.01). BANCR expression was significantly correlated with FIGO stage, pathological grade, myometrial invasion, and lymph node metastasis. The expression of BANCR was significantly correlated with that of MMP2/MMP1. In vitro, knockdown of BANCR significantly suppressed proliferation, migration, and invasion of Ishikawa and HEC-1A cells, and significantly inhibited the ERK/MAPK signaling pathway that decreased MMP2 and MMP1 expression.
CONCLUSION: BANCR is highly expressed in type 1 EC tissue and promotes EC-cell proliferation, migration, and invasion by activating ERK/MAPK signaling pathway that regulates MMP2/MMP1 expression. BANCR is expected to become a prognostic marker and therapeutic target in type 1 EC.

El-Aarag B, Kasai T, Masuda J, et al.
Anticancer effects of novel thalidomide analogs in A549 cells through inhibition of vascular endothelial growth factor and matrix metalloproteinase-2.
Biomed Pharmacother. 2017; 85:549-555 [PubMed] Related Publications
Lung cancer is one of the major causes of cancer-related mortality worldwide, and non-small-cell lung cancer is the most common form of lung cancer. Several studies had shown that thalidomide has potential for prevention and therapy of cancer. Therefore, the current study aimed to investigate the antitumor effects of two novel thalidomide analogs in human lung cancer A549 cells. The antiproliferative, antimigratory, and apoptotic effects in A549 cells induced by thalidomide analogs were examined. In addition, their effects on the expression of mRNAs encoding vascular endothelial growth factor165 (VEGF165) and matrix metalloproteinase-2 (MMP-2) were evaluated. Their influence on the tumor volume in nude mice was also determined. Results revealed that thalidomide analogs exhibited antiproliferative, antimigratory, and apoptotic activities with more pronounced effect than thalidomide drug. Furthermore, analogs 1 and 2 suppressed the expression levels of VEGF165 by 42% and 53.2% and those of MMP-2 by 45% and 52%, respectively. Thalidomide analogs 1 and 2 also reduced the tumor volume by 30.11% and 53.52%, respectively. Therefore, this study provides evidence that thalidomide analogs may serve as a new therapeutic option for treating lung cancer.

Rahman FU, Ali A, Khan IU, et al.
Novel phenylenediamine bridged mixed ligands dimetallic square planner Pt(II) complex inhibits MMPs expression via p53 and caspase-dependent signaling and suppress cancer metastasis and invasion.
Eur J Med Chem. 2017; 125:1064-1075 [PubMed] Related Publications
Novel phenylenediamine bridged mixed ligands dimetallic square planner Pt(II) complex (L-Pt-Py) was synthesized from simple commercially available precursors in good yield and characterized by (1)H, (13)C, 2D NOESY NMR and high resolution mass spectrometry (HR-ESI-MS). The stability of L-Pt-Py was checked by (1)H NMR in mixed DMSO-d6/D2O solvents. L-Pt-Py showed considerable in vitro cytotoxicity in lung (A549), breast (MCF-7) and liver (HepG2) cancer cell lines and strong in vivo growth inhibition in Escherichia coli (E. coli). These results were compared to the well-known market available platinum anticancer drug cisplatin. L-Pt-Py has strong ability to suppress the growth of multiple cancer cells. Mechanistically, it enhanced p53 protein expression and regulated p53-dependent genes expression such as p21, PUMA, MYC and hTERT. The TUNEL assay showed that L-Pt-Py induced cell death in cancer cells. Inhibition of caspase signaling with caspase inhibitor Z-VAD-FMK suggested that cell death induced by this complex was caspase-dependent. Importantly, L-Pt-Py has the ability to suppress the invasion and migration of human lung and luminal-like breast cancer cells. Similarly L-Pt-Py suppressed the expression of several matrix metalloproteinases (MMPs) such as MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9 to inhibit lung and breast cancer cell metastasis. L-Pt-Py showed stronger inhibitory effects on bacterial growth and also resulted in filamentous morphology of bacterial cells. The gel electrophoresis study of DNA migration revealed the strong interaction of L-Pt-Py with DNA. Taken altogether, L-Pt-Py was highly stable and the in vitro and in vivo biological study results corroborated this complex to be effective anticancer agent.

Kamata YU, Sumida T, Kobayashi Y, et al.
Introduction of ID2 Enhances Invasiveness in ID2-null Oral Squamous Cell Carcinoma Cells via the SNAIL Axis.
Cancer Genomics Proteomics. 2016 11-12; 13(6):493-497 [PubMed] Free Access to Full Article Related Publications
AIM: Inhibitor of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors that generally stimulate cell proliferation and inhibit differentiation. However, the role of ID2 in cancer progression remains ambiguous. Here, we investigated the function of ID2 in ID2-null oral squamous cell carcinoma (OSCC) cells.
MATERIALS AND METHODS: We introduced an ID2 cDNA construct into ID2-null OSCC cells and compared them with empty-vector-transfected cells in terms of cell proliferation, invasion, and activity and expression of matrix metalloproteinase (MMP).
RESULTS: ID2 introduction resulted in enhanced malignant phenotypes. The ID2-expressing cells showed increased N-cadherin, vimentin, and E-cadherin expression and epithelial-mesenchymal transition. In addition, cell invasion drastically increased with increased expression and activity of MMP2. Immunoprecipitation revealed a direct interaction between ID2 and zinc finger transcription factor, snail family transcriptional repressor 1 (SNAIL1).
CONCLUSION: ID2 expression triggered a malignant phenotype, especially of invasive properties, through the ID2-SNAIL axis. Thus, ID2 represents a potential therapeutic target for OSCC.

Luo Y, Wu JY, Lu MH, et al.
Carvacrol Alleviates Prostate Cancer Cell Proliferation, Migration, and Invasion through Regulation of PI3K/Akt and MAPK Signaling Pathways.
Oxid Med Cell Longev. 2016; 2016:1469693 [PubMed] Free Access to Full Article Related Publications
TRPM7 is a potential therapeutic target for treatment of prostate cancer. In this study, we investigated the effects of nonselective TRPM7 inhibitor carvacrol on cell proliferation, migration, and invasion of prostate cancer PC-3 and DU145 cells. Our results showed that carvacrol blocked TRPM7-like currents in PC-3 and DU145 cells and reduced their proliferation, migration, and invasion. Moreover, carvacrol treatment significantly decreased MMP-2, p-Akt, and p-ERK1/2 protein expression and inhibited F-actin reorganization. Furthermore, consistently, TRPM7 knockdown reduced prostate cancer cell proliferation, migration, and invasion as well. Our study suggests that carvacrol may have therapeutic potential for the treatment of prostate cancer through its inhibition of TRPM7 channels and suppression of PI3K/Akt and MAPK signaling pathways.

Hsia TC, Yu CC, Hsiao YT, et al.
Cantharidin Impairs Cell Migration and Invasion of Human Lung Cancer NCI-H460 Cells via UPA and MAPK Signaling Pathways.
Anticancer Res. 2016; 36(11):5989-5997 [PubMed] Related Publications
Cantharidin (CTD), a component of natural mylabris (Mylabris phalerata Pallas), has been shown to have biological activities and induce cell death in many human cancer cells. In the present study, we investigated the effect of CTD on cell migration and invasion of NCI-H460 human lung cancer cells. Cell viability was examined and results indicated that CTD decreased the percentage of viable cells in dose-dependent manners. CTD inhibited cell migration and invasion in dose-dependent manners. Gelatin zymography analysis was used to measure the activities of matrix metalloproteinases (MMP-2/-9) and the results indicated that CTD inhibited the enzymatic activities of MMP-2/-9 of NCI-H460 cells. Western blotting was used to examine the protein expression of NCI-H460 cells after incubation with CTD and the results showed that CTD decreased the expression of MMP-2/-9, focal adhesion kinase (FAK), Ras homolog gene family, member A (Rho A), phospho-protein kinase B (AKT) (Thr308)(p-AKT(308)), phospho-extracellular signal-regulated kinase1/2 (p-ERK1/2), phospho-p38 mitogen-activated protein (MAP) kinase (p-p38), phospho c-Jun N-terminal kinase 1/2 (p-JNK1/2), nuclear factor-κB (NF-κB) and urokinase plasminogen activator (UPA). Furthermore, confocal laser microscopy was used to confirm that CTD suppressed the expression of NF-κB p65, but did not significantly affect protein kinase C (PKC) translocation in NCI-H460 cells. Based on those observations, we suggest that CTD may be used as a novel anticancer metastasis agent for lung cancer in the future.

Lu KH, Chen PN, Hsieh YH, et al.
3-Hydroxyflavone inhibits human osteosarcoma U2OS and 143B cells metastasis by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and reduces 143B tumor growth in vivo.
Food Chem Toxicol. 2016; 97:177-186 [PubMed] Related Publications
Many natural flavonoids have cytostatic and apoptotic properties; however, we little know whether the effect of synthetic 3-hydroxyflavone on metastasis and tumor growth of human osteosarcoma. Here, we tested the hypothesis that 3-hydroxyflavone suppresses human osteosarcoma cells metastasis and tumor growth. 3-hydroxyflavone, up to 50 μM without cytotoxicity, inhibited U2OS and 143B cells motility, invasiveness and migration by reducing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA) and also impaired cell adhesion to gelatin. 3-hydroxyflavone significantly reduced p-focal adhesion kinase (FAK) Tyr397, p-FAK Tyr925, p-steroid receptor coactivator (Src), p-mitogen/extracellular signal-regulated kinase (MEK)1/2, p-myosin light chain (MLC)2 Ser19, epithelial cell adhesion molecule, Ras homolog gene family (Rho)A and fibronectin expressions. 3-hydroxyflavone also affected the epithelial-mesenchymal transition (EMT) by down-regulating expressions of Vimentin and α-catenin with activation of the transcription factor Slug. In nude mice xenograft model and tail vein injection model showed that 3-hydroxyflavone reduced 143B tumor growth and lung metastasis. 3-hydroxyflavone possesses the anti-metastatic activity of U2OS and 143B cells by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and suppresses 143B tumor growth in vivo. This may lead to clinical trials of osteosarcoma chemotherapy to confirm the promising result in the future.

Eiro N, Fernandez-Gomez J, Sacristán R, et al.
Stromal factors involved in human prostate cancer development, progression and castration resistance.
J Cancer Res Clin Oncol. 2017; 143(2):351-359 [PubMed] Related Publications
PURPOSE: To detect new predictive markers from the prostate cancer tissue, to study the expression by cultured cancer-associated fibroblasts (CAFs) of stromal factors implicated in prostate carcinogenesis, and to compare their expressions in localized, metastatic, castration-sensitive (CSCP), castration-resistant prostate tumors (CRCP) as well as in fibroblasts from benign prostatic hyperplasia (BPH).
MATERIALS AND METHODS: The genomic expression of 20 stroma-derived factors, including the androgen receptor (AR), growth factors (FGF2, FGF7, FGF10, HGF, TGFβ, PDGFB), protein implicated in invasion (MMP-2, MMP-9 and MMP-11), inflammation (IL-6, IL-17, STAT-3 and NFκB), stroma/epithelium interaction (CDH11, FAP, CXCL12 and CXCL14) and chaperones (HPA1A and HSF1), was evaluated in cultured fibroblasts both from BHP and prostate carcinomas (PCa). After isolation and culture of fibroblasts by biopsy specimens, RNA was isolated and genomic studies performed.
RESULTS: Finally, 5 BPH and 37 PCa specimens were selected: clinically localized (19), metastatic (5), CSCP (7) and CRPC (6). Interleukin-17 receptor (IL-17RB) was highly expressed in CAFs compared with fibroblasts from BPH. However, metalloproteinase-2 and chemokine ligand 14 (CXCL14) were expressed at higher levels by fibroblasts from BPH. The fibroblastic growth factor-7 was highly expressed by CAFs from localized tumors, but metalloproteinase-11 in metastatic tumors. MMP-11, androgen receptor (AR) and heat-shock-70kda-protein-1A (HSPA1A) expressions were significantly higher in CAFs from CRPC.
CONCLUSIONS: These results demonstrate a CAFs heterogeneity among prostate carcinomas with regard to some molecular profile expressions that may be relevant in tumor development (IL-17RB), progression (MMP-11) and castration resistance (AR, MMP-11 and HSPA1A).

Zhou JX, Zhou L, Li QJ, et al.
Association between high levels of Notch3 expression and high invasion and poor overall survival rates in pancreatic ductal adenocarcinoma.
Oncol Rep. 2016; 36(5):2893-2901 [PubMed] Related Publications
Pancreatic ductal adenocarcinoma (PDAC) is a commonly fatal tumour. It is characterized by early metastasis and high mortality. Many patients die as a result of PDAC tumour progression. However, the underlying mechanism of invasion and metastasis in PDAC is still not fully understood. Previous studies showed that the Notch signalling pathway may play an important role in the progression of tumour invasion and metastasis. However, it is not yet known whether the Notch signalling pathway participates in the progression of invasion in PDAC. In the present study, immunohistochemistry showed that a high expression of Notch3 was correlated with tumour grade, metastasis, venous invasion and American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) stage. Kaplan-Meier curves suggested that a high expression of Notch3 was a significant risk factor for shortened survival time. We also showed that inhibition of Notch3 had an anti‑invasion role in PDAC cells. In vitro, the inhibition of Notch3 reduced the migration and invasion capabilities of PDAC cells by regulating the expressions of E-cadherin, CD44v6, MMP-2, MMP-9, VEGF and uPA via regulating the COX-2 and ERK1/2 pathways. These results indicated that downregulation of the Notch signalling pathway may be a novel and useful approach for preventing and treating PDAC invasion.

Kim BR, Kang MH, Kim JL, et al.
RUNX3 inhibits the metastasis and angiogenesis of colorectal cancer.
Oncol Rep. 2016; 36(5):2601-2608 [PubMed] Related Publications
Recent studies have determined that inactivation of runt‑related transcription factor 3 (RUNX3) expression is highly associated with lymph node metastasis and poor prognosis in various types of cancer. However, the mechanism of RUNX3-mediated suppression of tumor metastasis remains unclear. Herein, we aimed to clarify the effect of RUNX3 on metastasis and angiogenesis in colorectal cancer (CRC). Firstly, we found that the reduction in expression of RUNX3 in CRC tissues when compared with tumor adjacent normal colon tissues, as indicated by reduced RUNX3 staining, was significantly correlated with tumor-node-metastasis (TNM) stage. Secondly, we demonstrated that RUNX3 overexpression inhibited CRC cell migration and invasion resulting from the upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression. In contrast, the knockdown of RUNX3 reduced the inhibition of migration and invasion of CRC cells. Finally, we found that restoration of RUNX3 decreased vascular endothelial growth factor (VEGF) secretion and suppressed endothelial cell growth and tube formation in CRC cells. All in all, our findings may provide insight into the development of RUNX3 for CRC metastasis diagnostics and therapeutics.

Cho Y, Cho EJ, Lee JH, et al.
Fucoidan-induced ID-1 suppression inhibits the in vitro and in vivo invasion of hepatocellular carcinoma cells.
Biomed Pharmacother. 2016; 83:607-616 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) is a fast growing tumor associated with a high tendency for vascular invasion and distant metastasis. Recently, we reported that fucoidan displays inhibitory effect on proliferation and invasion of HCC cells. In this study, we investigated the anti-metastatic effect of fucoidan on HCC cells and the key signal that modulates metastasis. The anti-metastatic effect of fucoidan was evaluated in vitro using an invasion assay with human HCC cells (Huh-7, SNU-761, and SNU-3085) under both normoxic (20% O2 and 5% CO2, at 37°C) and hypoxic (1% O2, 5% CO2, and 94% N2, at 37°C) conditions. Complementary DNA (cDNA) microarray analysis was performed to find the molecule which is significantly suppressed by fucoidan. In vivo study using a distant metastasis model by injecting SNU-761 cells into spleen via portal vein was performed to confirm the inhibitory effect by small interfering RNA (siRNA) transfection. Immunoblot analyses were used to investigate the signaling pathway. Fucoidan significantly suppressed the invasion of human HCC cells (Huh-7, SNU-761, and SNU-3085). Using cDNA microarray analysis, we found the molecule, ID-1, which was significantly suppressed by fucoidan treatment. Downregulation of ID-1 by siRNA significantly decreased invasion of HCC cells, both in vitro and in vivo (both P<0.05) in a NDRG-1/CAP43-dependent manner. In immunoblot assay, downregulation of ID-1 by siRNA decreased the expressions of epithelial-mesenchymal transition markers including CK19, vimentin, MMP2, and fibronectin. Immunofluorescence study also revealed that actin rearrangement was inhibited when ID-1 was down-regulated in HCC cells. Interestingly, in SNU-761 cells, the ID-1 expressions under hypoxic conditions were lower as compared to those under normoxic conditions. Under hypoxic conditions, HIF-1α up-regulated NDRG-1/CAP43, while HIF-2α down-regulated ID-1, which might be a compensatory phenomenon against hypoxia-induced HCC invasion. In conclusion, NDRG-1/CAP43-dependent down-regulation of ID-1 suppressed HCC invasion both in vitro and in vivo, which was modulated by fucoidan treatment. Moreover, the compensatory down-regulation of ID-1 against hypoxia-induced HCC invasion was observed. ID-1 is a novel therapeutic target for the treatment of metastatic HCC.

Ji GH, Cui Y, Yu H, Cui XB
Profiling analysis of FOX gene family members identified FOXE1 as potential regulator of NSCLC development.
Cell Mol Biol (Noisy-le-grand). 2016; 62(11):57-62 [PubMed] Related Publications
Lung cancer is one of the most malignant tumors worldwide with a high mortality rate, which has not been improved since several decades ago. FOX gene family members have been reported to play extensive roles in regulating many biological processes and disorders. In order to clarify the contribution of FOX gene family members in lung cancer biology, we performed expression profiling analysis of FOX gene family members from FOXA to FOXR in lung cancer cell lines and tissue specimens by Real-time PCR, western blot and immunohistochemistry analysis. We found that FOXE1 was the only gene which was over-expressed in six out of eight lung cancer cell lines and human cancer tissue specimens (28 out of 35 cases with higher expression and 7 out of 35 cases with moderate expression). Further investigation showed that MMP2 gene was up-regulated, and autophagy markers such as LC3B, ATG5, ATG12 and BECLIN1, were down-regulated concomitant with the increase of FOXE1. These results implicated that FOXE1 may be an important regulator by targeting autophagy and MMPs pathways in lung cancer development.

Karam RA, Al Jiffry BO, Al Saeed M, et al.
DNA repair genes polymorphisms and risk of colorectal cancer in Saudi patients.
Arab J Gastroenterol. 2016; 17(3):117-120 [PubMed] Related Publications
BACKGROUND AND STUDY AIMS: Polymorphisms in the DNA repair genes may influence individual capacity to repair DNA damage, which may be associated with increased genetic instability and carcinogenesis. Our aim was to evaluate the relation of genetic polymorphisms in 2 DNA repair genes, XPD Lys751Gln and XRCC1 (A399G), with colorectal cancer (CRC) susceptibility. We further investigated the potential effect of these DNA repair variants on clinicopathological parameters of CRC patients.
PATIENTS AND METHODS: Both XPD and XRCC1 polymorphisms were characterised in one hundred CRC patients and one hundred healthy controls who had no history of any malignancy by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and PCR with confronting two-pair primers (PCR-CTPP), using DNA from peripheral blood in a case control study.
RESULTS: Our results revealed that the frequencies of GG genotype of XRCC1 399 polymorphism were significantly higher in the CRC patients than in the normal individuals (p⩽0.03), and did not observe any association between the XPD Lys751Gln polymorphism and CRC risk. We found association between both XRCC1 A399G polymorphisms and histological grading of disease.
CONCLUSION: Our results suggested that, XRCC1 gene is an important candidate gene for susceptibility to colorectal carcinoma.

Zhou Y, Han Y, Zhang Z, et al.
MicroRNA-124 upregulation inhibits proliferation and invasion of osteosarcoma cells by targeting sphingosine kinase 1.
Hum Cell. 2017; 30(1):30-40 [PubMed] Related Publications
Increasing evidence has confirmed that the dysregulation of microRNAs (miRNAs) contributes to the proliferation and invasion of human cancers. Previous studies have shown that the dysregulation of miR-124 is in numerous cancers. However, the roles of miR-124 in human osteosarcoma (OS) have not been well clarified. Therefore, this study was to investigate the biological functions and molecular mechanisms of miR-124 in OS cell lines, discussing whether it could be a therapeutic biomarker of OS in the future. In this study, our results demonstrated that miR-124 was down-regulated in OS cell lines and tissues. Furthermore, the low level of miR-124 was associated with increased expression of Sphingosine kinase 1 (SPHK1) in OS cells and tissues. Up-regulation of miR-124 significantly inhibited cell proliferation, invasion, and MMP-2 and -9 expressions of OS cells. Bioinformatics analysis predicted that the SPHK1 was a potential target of miR-124. Further study by luciferase reporter assay demonstrated that miR-124 could directly target SPHK1. Overexpression of SPHK1 in OS cells transfected with miR-124 mimic partially reversed the inhibitory of miR-124. In conclusion, miR-124 inhibited cell proliferation and invasion in OS cells by downregulation of SPHK1, and that downregulation of SPHK1 was essential for the miR-124-inhibited cell invasion and in OS cells.

Li Z, Wei D, Yang C, et al.
Overexpression of long noncoding RNA, NEAT1 promotes cell proliferation, invasion and migration in endometrial endometrioid adenocarcinoma.
Biomed Pharmacother. 2016; 84:244-251 [PubMed] Related Publications
Long noncoding RNAs (lncRNAs) are emerging as important modulators in the biological processes and tumorigenesis. However, whether lncRNAs are involved in endometrial endometrioid adenocarcinoma (EEC) remains unclear. In the present study, we explored the expression pattern, clinical significance and biological function of nuclear enriched abundant transcript 1 (NEAT1) in EEC. The expression levels of NEAT1 were elevated in EEC tissues and cell lines, and higher expression levels of NEAT1 were positively correlated with FIGO stage and lymph node metastasis. Overexpression of NEAT1 in HEC-59 cells transfected with pGCMV-NEAT1 promotes cell growth, colony formation ability as well as invasive and migratory ability; while knock-down of NEAT1 in HEC-59 cells by siNEAT1 transfection exhibited the opposite effects. Flow cytometry analysis showed that overexpression of NEAT1 led to an increase in S-phase cells and attenuated cell apoptosis, and knock-down of NEAT1 induced G0/G1 arrest and also induced cell apoptosis in HEC-59 cells. Tumor metastasis real-time PRC array showed that six metastasis-related genes (c-myc, insulin like growth factor 1(IGF1), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 7(MMP-7) were up-regulated, and Cadherin 1 and TIMP metallopeptidase inhibitor 2 were down-regulated) in NEAT1-overexpressing HEC-59 cells. Further qRT-PCR and western blot results confirmed that c-myc, IFG1, MMP-2 and MMP-7 were dys-regulated by NEAT1. Together, our data underscore the significance of NEAT1 in EEC development, and NEAT1 may a potential therapeutic target for EEC.

Gui F, Hong Z, You Z, et al.
MiR-21 inhibitor suppressed the progression of retinoblastoma via the modulation of PTEN/PI3K/AKT pathway.
Cell Biol Int. 2016; 40(12):1294-1302 [PubMed] Related Publications
MicroRNA-21 (miR-21) was reported to act as an oncogene during the development of many human tumors. However, little was revealed about the function of miR-21 in retinoblastoma (RB). In this study, we examined the expression of miR-21 in RB tissues and explored the relationship between miR-21 and phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-OH kinase (PI3K)/AKT signal. Quantitative real-time PCR (qRT-PCR) results showed that the level of miR-21 in RB tissues was higher than that in retinal normal tissues. In Weri-Rb-1 cells, miR-21 inhibitor suppressed the expression of miR-21 and cell viability, but improved cell apoptotic rates by modulating the levels of PDCD4, Bax, and Bcl-2. Meanwhile, miR-21 inhibitor suppressed cell migration and invasion via inhibiting the protein levels of MMP2 and MMP9 and significantly affected the expression of PTEN, PI3K, and p-AKT. Taken together, miR-21 inhibitor suppressed cell proliferation, migration, and invasion via the PTEN/PI3K/AKT signal. These findings revealed the molecular basis of miR-21 functioning in the progression of RB and provided a new means for cell therapy in RB.

Guo XQ, Li XY
The expression and clinical significance of metastasis suppressor gene and matrix metalloproteinase-2 in esophageal squamous cell of carcinoma.
Pak J Pharm Sci. 2016; 29(4 Suppl):1339-42 [PubMed] Related Publications
To investigate the expression and clinical significance of metastasis suppressor gene and matrix metalloproteinase-2 in esophageal squamous cell of carcinoma. choose 30 cases of specimens of esophageal squamous cell carcinoma which are removed in surgery and confirmed by pathology and 30 cases of specimens of normal esophageal mucosa. Use immunohistochemistry SP method to detect the expression of nm23-H1, MMP-2 protein in esophageal squamous cell carcinoma and normal esophageal mucosal. The positive rate of nm23-H1 protein in esophageal squamous cell carcinoma was 43.3% (13/30), while that in normal esophageal mucosa was 100% (30/30), which has a significant difference between them (χ2=22. 083, P<0.05). The positive rate of MMP-2 protein in esophageal squamous cell carcinoma was 90.0% (27/30), while that in normal esophageal mucosa was 33.3% (10/30), and there is a significant difference between them (χ2=28. 370, P<0.05); For the expression of nm23-H1 and MMP-2 in esophageal squamous cell carcinoma, there was nothing to do with sex, age and tumor size (P>0.05), but it was related to the degree of tumor differentiation, depth of invasion and lymph node metastasis (P<0.05); The expression of nm23-H1 is related to the cut end of residual cancer (P<0.05), while the expression of MMP-2 has nothing to do with the cut end of residual cancer (P>0.05); The expression of nm23-H1 and MMP-2 in esophageal squamous cell carcinoma was negatively correlated. nm23-H1 and MMP-2 have played a role in the development of esophageal cancer, which can promote the occurence of distant metastasis; The loss of expression of nm23-H1 may be related to cut end residual cancer; nm23-H1 and MMP-2 may be as an indicator for esophageal cancer metastasis and prognosis.

Cao L, Liu J, Zhang L, et al.
Curcumin inhibits H2O2-induced invasion and migration of human pancreatic cancer via suppression of the ERK/NF-κB pathway.
Oncol Rep. 2016; 36(4):2245-51 [PubMed] Related Publications
Curcumin (diferuloylmethane), a natural polyphenol present in turmeric, possesses a wide spectrum of pharmacological properties, including antioxidant and antitumor metastatic activities. However, the underlying mechanisms by which curcumin suppresses the metastasis of pancreatic cancer are still not fully elucidated. Our previous study demonstrated that a moderate amount of hydrogen peroxide (H2O2) is able to promote pancreatic cancer invasion. The aim of this study was to determine whether curcumin can suppress H2O2-induced tumor invasive and migratory abilities. Human pancreatic cancer BxPC-3 and Panc-1 cells were exposed to H2O2 with or without curcumin or N-acetylcysteine (NAC; a scavenger of free radicals). The effects of curcumin on pancreatic cancer cell proliferation was analyzed using MTT assay. The intracellular reactive oxygen species (ROS) was determined using 2,7-dichlorodihydrofluorecein diacetate. The cellular invasive and migratory abilities were analyzed using Transwell Matrigel invasion assay and wound healing assay, respectively. The expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were determined using qT-PCR and western blotting at mRNA and protein level. The activation of p-extracellular signal-regulated kinase (ERK) and p-nuclear factor-κB (NF-κB) were measured by western blotting. Our data showed that curcumin inhibited cancer cell proliferation in a dose-dependent manner. Curcumin and NAC were able to inhibit H2O2-induced ROS production, reduce the migration and invasion, and decrease the expression of MMP-2 and MMP-9 in pancreatic cancer cells. In addition, the H2O2‑induced elevation of p-ERK and p-NF-κB in BxPC-3 and Panc-1 cells were reduced by curcumin, NAC and PD 98059 (an ERK inhibitor). These data indicate that curcumin suppresses pancreatic cancer migration and invasion through the inhibition of the ROS/ERK/NF-κB signaling pathway. This study suggests that curcumin may be a potential anticancer agent for pancreatic cancer.

Radunovic M, Nikolic N, Milenkovic S, et al.
The MMP-2 and MMP-9 promoter polymorphisms and susceptibility to salivary gland cancer.
J BUON. 2016 May-Jun; 21(3):597-602 [PubMed] Related Publications
PURPOSE: Matrix metalloproteinases (MMPs) are a family of endopeptidases that may play an important role in the development of salivary gland cancer (SGC). MMP-2 and MMP-9, members of the gelatinase protein family, are capable of degrading type IV collagen of basement membranes, and their overexpression is often associated with tumor aggressiveness and poor prognosis. The aim of this study was to establish the role of single nucleotide polymorphisms (SNPs) in MMP-2 and MMP-9 genes as putative susceptibility factors for the development of SGC.
METHODS: The MMP-2 -1306 C>T, MMP-2 -1575 G>A and MMP-9 -1562 C>T polymorphisms were analyzed in 93 SGC cases and 100 controls using PCR-RFLP.
RESULTS: The T allele for the MMP-2-1306 C>T polymorphism exhibited its effect in heterozygous carriers, increasing the risk for SGC (odds ratio/OR 1.98, 95% CI 1.07-3.65, p=0.03). According to the dominant model, CT+TT genotypes had a 2-fold increased risk of developing SGCs (p=0.02).When the dominant model was applied for the MMP2 -1575 G>A, individuals with GA+AA genotypes exhibited a 1.77-fold increase in cancer risk, but with borderline significance (p=0.049). Heterozygous carriers of the variant T allele for the MMP-9 -1562 C>T polymorphism had roughly a 2-fold increase in susceptibility for SGC compared to wild type homozygotes (CC) (p=0.02).
CONCLUSION: Our findings suggest MMP-2-1306 C>T and MMP-9-1562 C>T polymorphisms genotypes seem to influence the development of SGCs, whereas MMP-2 -1575 G>A seems to be of a minor importance.

Pohlig F, Ulrich J, Lenze U, et al.
Glucosamine sulfate suppresses the expression of matrix metalloproteinase-3 in osteosarcoma cells in vitro.
BMC Complement Altern Med. 2016; 16(1):313 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Glucosamine, a common dietary supplement, has a possible anti-sarcoma effect. However, an understanding of the underlying mechanism of such an effect is limited. For this study we hypothesized that glucosamine suppresses the basal level of matrix metalloproteinase expression in human osteosarcoma cell lines.
METHODS: We examined the osteosarcoma cell lines, MG-63 and SaOS-2. Cells were exposed to 0, 10, 50 and 100 μg/ml glucosamine sulfate for 48 h and treatment toxicity was determined through measurement of cell viability and proliferation. Relative gene expression of matrix metalloproteinase (MMP)-2, -3 and -9 was quantified by real-time polymerase chain reaction. Protein levels of MMP-2 and -9 were assessed by ELISA.
RESULTS: Administration of 10, 50 or 100 μg/ml glucosamine sulfate had no effect on the cell viability of MG-63 and SaOS-2 cells. A significant reduction of MMP expression in both cell lines was observed only for MMP-3, while a decrease in MMP-9 was seen in SaOS-2 cells. The expression of MMP-2 was not significantly affected in either cell line. Protein level of MMP-3 was reduced in both cell lines upon stimulation with 10 μg/ml glucosamine sulfate whereas for MMP-9 a decrease could only be observed in SaOS-2 cells.
CONCLUSION: In this study, we found a pronounced suppressive effect of glucosamine sulfate particularly on MMP-3 and also MMP-9 mRNA and protein levels in osteosarcoma cell lines in vitro. The data warrants further investigations into the potential anti-tumor efficacy of glucosamine sulfate in osteosarcoma.

Micocci KC, Moritz MN, Lino RL, et al.
ADAM9 silencing inhibits breast tumor cells transmigration through blood and lymphatic endothelial cells.
Biochimie. 2016 Sep-Oct; 128-129:174-82 [PubMed] Related Publications
ADAMs are transmembrane multifunctional proteins that contain disintegrin and metalloprotease domains. ADAMs act in a diverse set of biological processes, including fertilization, inflammatory responses, myogenesis, cell migration, cell proliferation and ectodomain cleavage of membrane proteins. These proteins also have additional functions in pathological processes as cancer and metastasis development. ADAM9 is a member of ADAM protein family that is overexpressed in several types of human carcinomas. The aim of this study was to investigate the role of ADAM9 in hematogenous and lymphatic tumor cell dissemination assisting the development of new therapeutic tools. The role of ADAM9 in the interaction of breast tumor cells (MDA-MB-231) and endothelial cells was studied through RNA silencing. ADAM9 silencing in MDA-MB-231 cells had no influence in expression of several genes related to the metastatic process such as ADAM10, ADAM12, ADAM17, cMYC, MMP9, VEGF-A, VEGF-C, osteopontin and collagen XVII. However, there was a minor decrease in ADAM15 expression but an increase in that of MMP2. Moreover, ADAM9 silencing had no effect in the adhesion of MDA-MB-231 cells to vascular (HMEC-1 and HUVEC) and lymphatic cells (HMVEC-dLyNeo) under flow condition. Nevertheless, siADAM9 in MDA-MB-231 decreased transendothelial cell migration in vitro through HUVEC, HMEC-1 and HMVEC-dLyNeo (50%, 40% and 32% respectively). These results suggest a role for ADAM9 on the extravasation step of the metastatic cascade through both blood and lymph vessels.

An J, Li Z, Dong Y, et al.
Methicillin-Resistant Staphylococcus Aureus infection exacerbates NSCLC cell metastasis by up-regulating TLR4/MyD88 pathway.
Cell Mol Biol (Noisy-le-grand). 2016; 62(8):1-7 [PubMed] Related Publications
Methicillin-resistant Staphylococcus aureus (MRSA) infection is a major public health problem worldwide, which brings to a more great threat for cancer patients. It's necessary to give attentions to lung cancer combined with MRSA. This study mainly focuses on the influences of MRSA on lung cancer cells (A549). We first found that MRSA infection can enhance metastasis ability of A549 cell and increase matrix metalloproteinase (MMP2 and MMP9) expressions in MRSA-infected A549 cell. Toll-like receptors (TLRs) have been reported to play an important role in tumor cell initiation and migration, and regulate the expression of MMPs in tumors. Our further research indicates that Toll-like receptor 4 (TLR4)/molecules myeloid differentiation factor 88 (MyD88) signaling was up-regulated in MRSA-infected A549 cell. After silencing TLR4 or MyD88 gene, the enhanced metastasis ability of A549 cell by MRSA was decreased significantly; Also, MMP2 and MMP9 expression increase was reversed. In conclusion, MRSA infection can enhance NSCLC cell metastasis by up-regulating TLR4/MyD88 signaling.

Shin SS, Park SS, Hwang B, et al.
MicroRNA-106a suppresses proliferation, migration, and invasion of bladder cancer cells by modulating MAPK signaling, cell cycle regulators, and Ets-1-mediated MMP-2 expression.
Oncol Rep. 2016; 36(4):2421-9 [PubMed] Related Publications
Despite the clinical significance of tumorigenesis, little is known about the cellular signaling networks of microRNAs (miRs). Here we report a new finding that mir‑106a regulates the proliferation, migration, and invasion of bladder cancer cells. Basal expression levels of mir‑106a were significantly lower in bladder cancer cells than in normal urothelial cells. Overexpression of mir‑106a suppressed the proliferation of bladder cancer cell line EJ. Transient transfection of mir‑106a into EJ cells led to downregulation of ERK phosphorylation and upregulation of p38 and JNK phosphorylation over their levels in the control. Flow cytometry analysis revealed that mir‑106a-transfected cells accumulated in the G1-phase of the cell cycle, and cyclin D1 and CDK6 were significantly downregulated. This G1-phase cell cycle arrest was due in part to the upregulation of p21CIP1/WAF1. In addition, mir‑106a overexpression blocked the wound-healing migration and invasion of EJ cells. Furthermore, mir‑106a transfection resulted in decreased expression of MMP-2 and diminished binding activity of transcription factor Ets-1 in EJ cells. Collectively, we report the novel mir‑106a-mediated molecular signaling networks that regulate the proliferation, migration, and invasion of bladder cancer cells, suggesting that mir‑106a may be a therapeutic target for treating advanced bladder tumors.

Gong C, Yang Z, Wu F, et al.
miR-17 inhibits ovarian cancer cell peritoneal metastasis by targeting ITGA5 and ITGB1.
Oncol Rep. 2016; 36(4):2177-83 [PubMed] Related Publications
An essential step in the peritoneal spread of ovarian cancer is the adhesion and implantation of tumor cells to the mesothelium layer. Integrin α5 and β1 have been reported to mediate the initial adhesion process and to correlate with disease survival in ovarian cancer. However, the molecular mechanism of integrin α5β1 dysregulation in tumorigenesis and metastasis remained enigmatic. In the present study, using the US NCI60 database, we identified miR-17 as a candidate regulator targeting both integrin α5 and β1. The level of miR-17 was evidently inversely correlated with that of α5 and β1 in ovarian cancer cell lines. Specifically, miR-17 bound directly to the 3' untranslated region (3'UTR) of α5 and β1 and suppressed their expression. Forced expression of miR-17 led to markedly diminished adhesion and invasion of ovarian cancer cells in vitro, and notably reduced metastatic nodules inside the peritoneal cavity in in vivo SKOV3 xenografts model. Moreover, ectopic expression of miR-17 in ovarian cancer cells resulted in repressed ILK phosphorylation as well as decreased production of active matrix metalloproteinase-2 (MMP-2). Our results indicated that miR-17 hampered ovarian cancer peritoneal propagation by targeting integrin α5 and β1. These findings supported the utility of miR-17/α5β1 to be considered as valuable marker for metastatic potential of ovarian cancer cells, or a therapeutic target in ovarian cancer treatment.

Zhuang X, Qiao T, Xu G, et al.
Combination of nadroparin with radiotherapy results in powerful synergistic antitumor effects in lung adenocarcinoma A549 cells.
Oncol Rep. 2016; 36(4):2200-6 [PubMed] Related Publications
Low-molecular-weight heparins (LMWHs), which are commonly used in venous thromboprophylaxis and treatment, have recently been reported to have effects on cancer metastasis in pre-clinical research studies. This study was planned to define the synergistic antitumor effects of nadroparin (a kind of LMWH) combined with radiotherapy in A549 cells. Six experimental groups were set up in our study according to the different treatment: control group; irradiation (IR) group; low dose of nadroparin group (LMWH50, L50); high dose of nadroparin group (LMWH100, L100); LMWH50+IR group; LMWH100+IR group. The viability of A549 cells was assessed by Cell Counting Kit-8 (CCK-8) assay. The apoptosis of tumor cells was analyzed by flow cytometry (FCM) after treatment. The concentration of transforming growth factor-β1 (TGF-β1) in the culture supernatants was measured by enzyme-linked immunosorbent assay (ELISA). The migration and invasion of the A549 cells were tested by the Transwell chamber assay. The expression of survivin, CD147 and matrix metalloproteinase-2 (MMP-2) was analyzed by western blotting. CCK-8 assay showed that irradiation or nadroparin alone slightly inhibited the cell viability while the combined treatments significantly inhibited the cell viability in a dose- and time-dependent manner. The apoptosis rate showed greater improvement dose- and time‑dependently in the groups receiving combination therapy of nadroparin and irradiation than the control group or the group receiving nadroparin or irradiation alone by FCM. ELISA assay showed that the decreased TGF-β1 secretion was found after combined treatments with nadroparin and irradiation compared to either treatment alone. The Transwell chamber assay showed that nadroparin not only significantly suppressed the migration and invasion of A549 cells but also inhibited the enhanced ability of migration and invasion induced by X-ray irradiation. Western blotting showed that nadroparin inhibited the upregulated effects of survivin and MMP-2 expression induced by radiation in the combined treatment groups in a dose- and time-dependent manner. Moreover, the expression level of CD147 was the lowest in the combined treatment groups. This study identified that combination of nadroparin and irradiation had a strong synergistic antitumor effect in a dose- and time-related manner in vitro, which was reflected in the inhibition of cell viability, invasion and metastasis, promotion of apoptosis, inhibited secretion level of TGF-β1 and downregulation of CD147, MMP-2 and survivin expression.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. MMP2, Cancer Genetics Web: http://www.cancer-genetics.org/MMP2.htm Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 11 March, 2017     Cancer Genetics Web, Established 1999