Skip to main content
Top
Published in: Tumor Biology 9/2015

01-09-2015 | Research Article

Decreased MT1-MMP in gastric cancer suppressed cell migration and invasion via regulating MMPs and EMT

Authors: Wenfeng Li, Shouzhi Li, Liang Deng, Shibin Yang, Mingzhe Li, Shuo Long, Sile Chen, Fuxiang Lin, Longbin Xiao

Published in: Tumor Biology | Issue 9/2015

Login to get access

Abstract

Membrane type 1-matrix metalloproteinase (MT1-MMP) has been identified to play a significant role in several types of cancers, but little is known about the significance of MT1-MMP in gastric cancer patients. The purpose of this study is to investigate the involvement of MT1-MMP in tumor progression of gastric cancer. MT1-MMP expression levels were examined in gastric cancer tissues and cells, and normal gastric tissues and cells. The effects and molecular mechanisms of MT1-MMP expression on cell proliferation, migration, and invasion were also explored. In our results, MT1-MMP messenger RNA (mRNA) and protein expression levels were significantly increased in gastric cancer tissue. Moreover, the overexpression of MT1-MMP was positively associated with the status of clinical stage and lymph node metastasis through real-time PCR. Furthermore, knocking down MT1-MMP expression significantly suppressed the cell migration and invasion in vitro and regulated the expression of MMPs and epithelial-mesenchymal transition (EMT)-associated genes. In conclusions, our study demonstrates that MT1-MMP was overexpressed in gastric cancer tissue, and reduced expression of MT1-MMP suppressed cell migration, invasion, and through regulating the expression of MMPs and the process of EMT in gastric cancer.
Literature
1.
2.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: Globocan 2008. Int J Cancer J Int Cancer. 2010;127:2893–917.CrossRef Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: Globocan 2008. Int J Cancer J Int Cancer. 2010;127:2893–917.CrossRef
3.
go back to reference Jang BG, Kim WH. Molecular pathology of gastric carcinoma. Pathobiol J Immunopathol Mol Cell Biol. 2011;78:302–10.CrossRef Jang BG, Kim WH. Molecular pathology of gastric carcinoma. Pathobiol J Immunopathol Mol Cell Biol. 2011;78:302–10.CrossRef
4.
go back to reference Ohtsu A. Chemotherapy for metastatic gastric cancer: past, present, and future. J Gastroenterol. 2008;43:256–64.CrossRefPubMed Ohtsu A. Chemotherapy for metastatic gastric cancer: past, present, and future. J Gastroenterol. 2008;43:256–64.CrossRefPubMed
6.
go back to reference Suojanen J, Salo T, Koivunen E, Sorsa T, Pirila E. A novel and selective membrane type-1 matrix metalloproteinase (MT1-MMP) inhibitor reduces cancer cell motility and tumor growth. Cancer Biol Ther. 2009;8:2362–70.CrossRefPubMed Suojanen J, Salo T, Koivunen E, Sorsa T, Pirila E. A novel and selective membrane type-1 matrix metalloproteinase (MT1-MMP) inhibitor reduces cancer cell motility and tumor growth. Cancer Biol Ther. 2009;8:2362–70.CrossRefPubMed
7.
go back to reference Wang X, Wilson MJ, Slaton JW, Sinha AA, Ewing SL, Pei D. Increased aggressiveness of human prostate PC-3 tumor cells expressing cell surface localized membrane type-1 matrix metalloproteinase (MT1-MMP). J Androl. 2009;30:259–74.CrossRefPubMed Wang X, Wilson MJ, Slaton JW, Sinha AA, Ewing SL, Pei D. Increased aggressiveness of human prostate PC-3 tumor cells expressing cell surface localized membrane type-1 matrix metalloproteinase (MT1-MMP). J Androl. 2009;30:259–74.CrossRefPubMed
8.
go back to reference Akanuma N, Hoshino I, Akutsu Y, Murakami K, Isozaki Y, Maruyama T, et al. MicroRNA-133a regulates the mRNAs of two invadopodia-related proteins, FSCN1 and MMP14, in esophageal cancer. Br J Cancer. 2014;110:189–98.CrossRefPubMed Akanuma N, Hoshino I, Akutsu Y, Murakami K, Isozaki Y, Maruyama T, et al. MicroRNA-133a regulates the mRNAs of two invadopodia-related proteins, FSCN1 and MMP14, in esophageal cancer. Br J Cancer. 2014;110:189–98.CrossRefPubMed
9.
go back to reference Xu M, Wang YZ. miR-133a suppresses cell proliferation, migration and invasion in human lung cancer by targeting MMP-14. Oncol Rep. 2013;30:1398–404.PubMed Xu M, Wang YZ. miR-133a suppresses cell proliferation, migration and invasion in human lung cancer by targeting MMP-14. Oncol Rep. 2013;30:1398–404.PubMed
10.
go back to reference Liu Z, Yang H, Luo W, Jiang Q, Mai C, Chen Y, et al. Loss of cytoplasmic KLF4 expression is correlated with the progression and poor prognosis of nasopharyngeal carcinoma. Histopathology. 2013;63:362–70.CrossRefPubMed Liu Z, Yang H, Luo W, Jiang Q, Mai C, Chen Y, et al. Loss of cytoplasmic KLF4 expression is correlated with the progression and poor prognosis of nasopharyngeal carcinoma. Histopathology. 2013;63:362–70.CrossRefPubMed
11.
go back to reference Ulasov I, Yi R, Guo D, Sarvaiya P, Cobbs C. The emerging role of MMP14 in brain tumorigenesis and future therapeutics. Biochim Biophys Acta. 1846;2014:113–20. Ulasov I, Yi R, Guo D, Sarvaiya P, Cobbs C. The emerging role of MMP14 in brain tumorigenesis and future therapeutics. Biochim Biophys Acta. 1846;2014:113–20.
12.
go back to reference Zhou H, Wu A, Fu W, Lv Z, Zhang Z. Significance of semaphorin-3A and MMP-14 protein expression in non-small cell lung cancer. Oncol Lett. 2014;7:1395–400.PubMedPubMedCentral Zhou H, Wu A, Fu W, Lv Z, Zhang Z. Significance of semaphorin-3A and MMP-14 protein expression in non-small cell lung cancer. Oncol Lett. 2014;7:1395–400.PubMedPubMedCentral
13.
go back to reference Atkinson JM, Pennington CJ, Martin SW, Anikin VA, Mearns AJ, Loadman PM, et al. Membrane type matrix metalloproteinases (MMPs) show differential expression in non-small cell lung cancer (NSCLC) compared to normal lung: correlation of MMP-14 mRNA expression and proteolytic activity. Eur J Cancer (Oxford, England : 1990). 2007;43:1764–71.CrossRef Atkinson JM, Pennington CJ, Martin SW, Anikin VA, Mearns AJ, Loadman PM, et al. Membrane type matrix metalloproteinases (MMPs) show differential expression in non-small cell lung cancer (NSCLC) compared to normal lung: correlation of MMP-14 mRNA expression and proteolytic activity. Eur J Cancer (Oxford, England : 1990). 2007;43:1764–71.CrossRef
14.
go back to reference Haage A, Nam DH, Ge X, Schneider IC. Matrix metalloproteinase-14 is a mechanically regulated activator of secreted MMPs and invasion. Biochem Biophys Res Commun. 2014;450:213–8.CrossRefPubMed Haage A, Nam DH, Ge X, Schneider IC. Matrix metalloproteinase-14 is a mechanically regulated activator of secreted MMPs and invasion. Biochem Biophys Res Commun. 2014;450:213–8.CrossRefPubMed
15.
go back to reference Udayakumar TS, Chen ML, Bair EL, Von Bredow DC, Cress AE, Nagle RB, et al. Membrane type-1-matrix metalloproteinase expressed by prostate carcinoma cells cleaves human laminin-5 beta3 chain and induces cell migration. Cancer Res. 2003;63:2292–9.PubMed Udayakumar TS, Chen ML, Bair EL, Von Bredow DC, Cress AE, Nagle RB, et al. Membrane type-1-matrix metalloproteinase expressed by prostate carcinoma cells cleaves human laminin-5 beta3 chain and induces cell migration. Cancer Res. 2003;63:2292–9.PubMed
16.
go back to reference Munaut C, Noel A, Hougrand O, Foidart JM, Boniver J, Deprez M. Vascular endothelial growth factor expression correlates with matrix metalloproteinases MT1-MMP, MMP-2 and MMP-9 in human glioblastomas. Int J Cancer J Int Cancer. 2003;106:848–55.CrossRef Munaut C, Noel A, Hougrand O, Foidart JM, Boniver J, Deprez M. Vascular endothelial growth factor expression correlates with matrix metalloproteinases MT1-MMP, MMP-2 and MMP-9 in human glioblastomas. Int J Cancer J Int Cancer. 2003;106:848–55.CrossRef
17.
go back to reference Wang YZ, Wu KP, Wu AB, Yang ZC, Li JM, Mo YL, et al. MMP-14 overexpression correlates with poor prognosis in non-small cell lung cancer. Tumour Biol J Int Soc Oncodev Biol Med. 2014. Wang YZ, Wu KP, Wu AB, Yang ZC, Li JM, Mo YL, et al. MMP-14 overexpression correlates with poor prognosis in non-small cell lung cancer. Tumour Biol J Int Soc Oncodev Biol Med. 2014.
18.
go back to reference He L, Chu D, Li X, Zheng J, Liu S, Li J, et al. Matrix metalloproteinase-14 is a negative prognostic marker for patients with gastric cancer. Dig Dis Sci. 2013;58:1264–70.CrossRefPubMed He L, Chu D, Li X, Zheng J, Liu S, Li J, et al. Matrix metalloproteinase-14 is a negative prognostic marker for patients with gastric cancer. Dig Dis Sci. 2013;58:1264–70.CrossRefPubMed
19.
go back to reference Peng CW, Wang LW, Fang M, Yang GF, Li Y, Pang DW. Combined features based on MT1-MMP expression, CD11b + immunocytes density and LNR predict clinical outcomes of gastric cancer. J Transl Med. 2013;11:153.CrossRefPubMedPubMedCentral Peng CW, Wang LW, Fang M, Yang GF, Li Y, Pang DW. Combined features based on MT1-MMP expression, CD11b + immunocytes density and LNR predict clinical outcomes of gastric cancer. J Transl Med. 2013;11:153.CrossRefPubMedPubMedCentral
20.
go back to reference Tetu B, Brisson J, Wang CS, Lapointe H, Beaudry G, Blanchette C, et al. The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis. Breast Cancer Res BCR. 2006;8:R28.CrossRefPubMed Tetu B, Brisson J, Wang CS, Lapointe H, Beaudry G, Blanchette C, et al. The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis. Breast Cancer Res BCR. 2006;8:R28.CrossRefPubMed
21.
go back to reference Wang L, Yuan J, Tu Y, Mao X, He S, Fu G, et al. Co-expression of MMP-14 and MMP-19 predicts poor survival in human glioma. Clin Transl Oncol Off Publ Fed Spanish Oncol Soc Natl Cancer Inst Mexico. 2013;15:139–45. Wang L, Yuan J, Tu Y, Mao X, He S, Fu G, et al. Co-expression of MMP-14 and MMP-19 predicts poor survival in human glioma. Clin Transl Oncol Off Publ Fed Spanish Oncol Soc Natl Cancer Inst Mexico. 2013;15:139–45.
22.
go back to reference Yang B, Gao J, Rao Z, Shen Q. Clinicopathological and prognostic significance of α5β1-integrin and MMP-14 expressions in colorectal cancer. Neoplasma. 2013;60:254–61.CrossRefPubMed Yang B, Gao J, Rao Z, Shen Q. Clinicopathological and prognostic significance of α5β1-integrin and MMP-14 expressions in colorectal cancer. Neoplasma. 2013;60:254–61.CrossRefPubMed
23.
go back to reference Trudel D, Desmeules P, Turcotte S, Plante M, Gregoire J, Renaud MC, et al. Visual and automated assessment of matrix metalloproteinase-14 tissue expression for the evaluation of ovarian cancer prognosis. Mod Pathol Off J US Can Acad Pathol Inc. 2014;27:1394–404. Trudel D, Desmeules P, Turcotte S, Plante M, Gregoire J, Renaud MC, et al. Visual and automated assessment of matrix metalloproteinase-14 tissue expression for the evaluation of ovarian cancer prognosis. Mod Pathol Off J US Can Acad Pathol Inc. 2014;27:1394–404.
24.
go back to reference Trudel D, Fradet Y, Meyer F, Harel F, Tetu B. Membrane-type-1 matrix metalloproteinase, matrix metalloproteinase 2, and tissue inhibitor of matrix proteinase 2 in prostate cancer: identification of patients with poor prognosis by immunohistochemistry. Hum Pathol. 2008;39:731–9.CrossRefPubMed Trudel D, Fradet Y, Meyer F, Harel F, Tetu B. Membrane-type-1 matrix metalloproteinase, matrix metalloproteinase 2, and tissue inhibitor of matrix proteinase 2 in prostate cancer: identification of patients with poor prognosis by immunohistochemistry. Hum Pathol. 2008;39:731–9.CrossRefPubMed
25.
go back to reference Wu KP, Li Q, Lin FX, Li J, Wu LM, Li W, et al. MT1-MMP is not a good prognosticator of cancer survival: evidence from 11 studies. Tumour Biol J Int Soc Oncodev Biol Med. 2014. Wu KP, Li Q, Lin FX, Li J, Wu LM, Li W, et al. MT1-MMP is not a good prognosticator of cancer survival: evidence from 11 studies. Tumour Biol J Int Soc Oncodev Biol Med. 2014.
26.
go back to reference Nishida Y, Miyamori H, Thompson EW, Takino T, Endo Y, Sato H. Activation of matrix metalloproteinase-2 (MMP-2) by membrane type 1 matrix metalloproteinase through an artificial receptor for proMMP-2 generates active MMP-2. Cancer Res. 2008;68:9096–104.CrossRefPubMed Nishida Y, Miyamori H, Thompson EW, Takino T, Endo Y, Sato H. Activation of matrix metalloproteinase-2 (MMP-2) by membrane type 1 matrix metalloproteinase through an artificial receptor for proMMP-2 generates active MMP-2. Cancer Res. 2008;68:9096–104.CrossRefPubMed
27.
go back to reference Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, et al. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 1994;370:61–5.CrossRefPubMed Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, et al. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 1994;370:61–5.CrossRefPubMed
28.
go back to reference Sato H, Takino T, Miyamori H. Roles of membrane-type matrix metalloproteinase-1 in tumor invasion and metastasis. Cancer Sci. 2005;96:212–7.CrossRefPubMed Sato H, Takino T, Miyamori H. Roles of membrane-type matrix metalloproteinase-1 in tumor invasion and metastasis. Cancer Sci. 2005;96:212–7.CrossRefPubMed
29.
go back to reference McGowan PM, Duffy MJ. Matrix metalloproteinase expression and outcome in patients with breast cancer: analysis of a published database. Ann Oncol Off J Eur Soc Med Oncol / ESMO. 2008;19:1566–72.CrossRef McGowan PM, Duffy MJ. Matrix metalloproteinase expression and outcome in patients with breast cancer: analysis of a published database. Ann Oncol Off J Eur Soc Med Oncol / ESMO. 2008;19:1566–72.CrossRef
30.
go back to reference Chellaiah MA, Ma T. Membrane localization of membrane type 1 matrix metalloproteinase by CD44 regulates the activation of pro-matrix metalloproteinase 9 in osteoclasts. BioMed Res Int. 2013;2013:302392.CrossRefPubMedPubMedCentral Chellaiah MA, Ma T. Membrane localization of membrane type 1 matrix metalloproteinase by CD44 regulates the activation of pro-matrix metalloproteinase 9 in osteoclasts. BioMed Res Int. 2013;2013:302392.CrossRefPubMedPubMedCentral
31.
go back to reference Knauper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, Stanton H, et al. Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem. 1996;271:17124–31.CrossRefPubMed Knauper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, Stanton H, et al. Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem. 1996;271:17124–31.CrossRefPubMed
32.
go back to reference Yang CC, Zhu LF, Xu XH, Ning TY, Ye JH, Liu LK. Membrane type 1 matrix metalloproteinase induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells. BMC Cancer. 2013;13:171.CrossRefPubMedPubMedCentral Yang CC, Zhu LF, Xu XH, Ning TY, Ye JH, Liu LK. Membrane type 1 matrix metalloproteinase induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells. BMC Cancer. 2013;13:171.CrossRefPubMedPubMedCentral
Metadata
Title
Decreased MT1-MMP in gastric cancer suppressed cell migration and invasion via regulating MMPs and EMT
Authors
Wenfeng Li
Shouzhi Li
Liang Deng
Shibin Yang
Mingzhe Li
Shuo Long
Sile Chen
Fuxiang Lin
Longbin Xiao
Publication date
01-09-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 9/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3381-7

Other articles of this Issue 9/2015

Tumor Biology 9/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine