Abstract
Matrilysin is a member of the matrix metalloproteinase gene family which is believed to play an important role in tumor progression. Expression of matrilysin mRNA was examined by reverse transcription-poly-merase chain reaction combined with Southern blot analysis in 46 human primary gastric cancers. Overexpression of matrilysin was observed in 28 (61%) of gastric cancer tissues. The positive expression ratio of matrilysin was significantly higher in the gastric cancers of subserosa or beyond it than in those within the submucosal layer. Immunohistochemical study with anti-matrilysin monoclonal antibody revealed that matrilysin was mainly expressed on cancer cells but not or very weakly expressed on other cells. In addition, an activated form of matrilysin detected by zymographic analysis was observed in gastric cancer tissues whereas none was detected in non-cancerous tissues, suggesting that matrilysin may directly and powerfully contribute to the invasion step of human gastr ic cancer. In order to gain more insight into the relationship of this metalloproteinase to invasive activity, we also modulated the expression of matrilysin in gastric cancer cells by DNA transfection using gastric cancer cell lines. Overexpression of matrilysin rendered the gastric cancer cells more invasive in vitro. Concomitant with clinical investigations, matrilysin may be an important metalloproteinase in the progression of gastric cancer. © Rapid Science Ltd.
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References
Liotta LA and Stetler-Stevenson WG, 1990, Metalloproteinases and cancer invasion. Semin Cancer Biol, 199-106.
Goldberg GI and Eisen AZ, 1991, Extracellular matrix metalloproteinases in tumor invasion and metastasis. Cancer Treat Res, 53421-40.
Declerck YA, Perez N, Shimada H, et al.1992, Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases. Cancer Res, 52701-8.
Tsuchiya Y, Sato H, Endo Y, et al.1993, Tissue inhibitor of metalloproteinases 1 is a negative regulator of the metastatic ability of a human gastric cancer cell line, KKLS, in the chick embryo. Cancer Res, 531397-402.
Bernhard EJ, Gruber SB and Muschel RJ, 1994, Direct evidence linking expression of matrix metalloproteinases 9 (92-kDa gelatinase/collagenase) to the metastatic phenotype in transformed rat embryo cells. Proc Natl Acad Sci, 914293-7.
Quantin B, Murphy G and Breathnach R, 1989, Pump-1 cDNA codes for a protein with characteristics similar to those of classical collagenase family members. Biochemistry, 285327-34.
Miyazaki K, Hattori Y, Umenishi F, Yasumitsu H and Umeda M, 1990, Purification and characterization of extracellular matrix-degrading metalloproteinase, matrin (pump-1), secreted from human rectal carcinoma cell line. Cancer Res, 507758-64.
Powell WC, Knox JD, Navre M, et al.1993, Expression of metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice. Cancer Res, 53417-22.
Kohn EC and Liotta LA, 1995, Molecular insight into cancer invasion: strategies for prevention and intervention. Cancer Res, 551856-62.
McDonell S, Wright JH, Gaire M and Matrisian LM, 1994, Expression and regulation of stromelysin and matrilysin by growth factors and oncogenes. Biochem SocTrans, 2258-63.
Knox JD and Wolf C, 1996, Matrilysin expression in human prostate carcinoma. Mol Carcinog, 1557-63.
Yoshimoto M, Itoh F, Yachi A, et al.1993, Expression of MMP-7 (pump-1) mRNA in human colorectal cancers. Int J Cancer, 54614-18.
Yamamoto H, Itoh F, Imai K, et al.1994, Expression of matrilysin mRNA in colorectal adenomas and its induction by truncated fibronectin. Biochem Biophys Res Commun, 201657-64.
Woessner JF Jr, 1991, Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J, 52145-54.
Itoh F, Yamamoto H, Hinoda Y and Imai K, 1996, Enhanced secretion and activation of matrilysin during9 malignant conversion of human colorectal epithelium and its relationship with invasive potential of colon cancer cells. Cancer, 771717-21.
Yamamoto H, Itoh F, Hinoda Y and Imai K, 1995, Suppression of matrilysin inhibits colon cancer cell invasion in vitro. Int J Cancer, 61218-22.
Otani Y, Okazaki I, Arai M, et al.1994, Gene expression of interstitial collagenase (matrix metalloproteinase 1) in gastrointestinal tract cancers. J Gastroenterol, 29391-7.
Nomura H, Fujimoto N, Seiki M, Mai M and Okada Y, 1996, Enhanced production of matrix metalloproteinases and activation of matrix metalloproteinase 2 (Gelatinase A) in human gastric carcinomas. Int J Cancer, 699-16.
Nomura H, Sato H, Seiki M, Mai M and Okada Y, 1995, Expression of membrane-type matrix metalloproteinase in human gastric carcinomas. Cancer Res, 553263-6.
McDonnel S, Navre M, Coffey JR and Matrisian LM, 1991, Expression and localization of the matrix metalloproteinase pump-1 (MMP-7) in human gastric and colon carcinomas. Mol Carcinog, 4527-33.
Chomczynski P and Sacchi N, 1987, Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analyt Biochem, 162156-9.
Sato Y, Mukai K, Watanabe S, Goto M and Shimosato Y, 1986, The AMeX method: a simplified technique of tissue-processing and paraffin-embedding with improved preservation of antigens for immunostaining. Am J Pathol, 125431-5.
Muller D, Quantin B, Gesnel MC, et al.1988, The collagenase gene family in humans consists of at least four members. Biochem J, 253187-92.
Nakajima-Iijima S, Hamada H, Reddy P and Kakunaga T, 1985, Molecular structure of the human cytoplasmic b-actin gene: interspecies homology of sequences in the introns. Proc Natl Acad Sci, 826133-7.
Sanger F, Nicklen S and Coulson AP, 1977, DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci, 745463-7.
Chen C and Okayama H, 1987, High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol, 72745-52.
Hendrix MJC, Seftor EA, Seftor REB and Fidler IJ, 1987, A simple quantitative assay for studying the invasive potential of high and low human metastatic variants. Cancer Lett, 38137-47.
Yamamoto H, Itoh F, Senota A, et al.1995, Expression of matrix metalloproteinase matrilysin (MMP-7) was induced by activated Ki-ras via AP-1 activation in SW1417 colon cancer cells. J. Clin Lab Anal, 9297-301.
Mayer B, Johnson JP, Leitl F, et al.1993, E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res, 531690-5.
Yamamoto H, Itoh F, Hinoda Y and Imai K, 1996, Inverse association of cell adhesion regulator messenger RNA expression with metastasis in human colorectal cancer. Cancer Res, 563605-9.
Miyazaki K, Kikkawa Y, Nakamura A, et al.1993, A large cell-adhesive scatter factor secreted by human gastric carcinoma cells. Proc Natl Acad Sci, 9011767-71.
Hakomori S, 1996, Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. Cancer Res, 565509-18.
Liotta LA, Steeg PS and Stetler-Stevenson WG, 1991, Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell, 64327-36.
Baragi VM, Fliszar CJ, Conroy MC, et al.1994, Contribution of the C-terminal domain of metalloproteinases to binding by tissue inhibitor of metalloproteinases. C-terminal truncated stromelysin and matrilysin exhibit compromised binding affinities as compared to full-length stromelysin. J Biol Chem, 26912692-7.
Koshikawa N, Yasumitsu H, Umeda M and Miyazaki K, 1992, Multiple secretion of matrix serine proteinases by human gastric carcinoma cell lines. Cancer Res, 525046-53.
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Senota, A., Itoh, F., Yamamoto, H. et al. Relation of matrilysin messenger RNA expression with invasive activity in human gastric cancer. Clin Exp Metastasis 16, 313–321 (1998). https://doi.org/10.1023/A:1006509312674
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DOI: https://doi.org/10.1023/A:1006509312674