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Host expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in normal colon tissue affects metastatic potential of colorectal cancer

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Diseases of the Colon & Rectum

Abstract

PURPOSE: To clarify the mechanism of cancer cell invasion, we paid close attention to the role of matrix metalloproteinases and tissue inhibitors of metalloproteinases in normal tissue that is located in the same organ as the cancer. METHODS: Samples were obtained from a tumor lesion and normal tissue in the resected large intestine of 59 patients with colorectal cancer, including 13 cases with liver metastasis (Group A) and 46 cases without liver metastasis (Group B). In each sample the expression of m-RNA for matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 was examined using reverse transcription-coupled polymerase chain reaction and southern hybridization. RESULTS: In normal colon tissue the expression rate of matrix metalloproteinase-2 in Group A (76.9 percent) was significantly higher than that of Group B (15.2 percent;P<0.0001). Regarding the expression pattern of m-RNA of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in normal colon tissue, Group B included 24 cases with matrix metalloproteinase-2 negative, and tissue inhibitor of metalloproteinase-2 positive (24/46; 52.2 percent). Conversely, Group A had only one case with matrix metalloproteinase-2 negative and tissue inhibitor of metalloproteinase-2 positive (1/13; 7.7 percent;P=0.0107). In addition, the ratio of cases with matrix metalloproteinase-2 positive and tissue inhibitor of metalloproteinase-2 negative in Group A was 30.8 percent (4/13), which was a significantly higher rate than that in Group B (3/46; 6.5 percent;P=0.0170). CONCLUSION: We think that the expression pattern of m-RNA of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in normal colon tissue is closely related to liver metastasis in colon cancer patients.

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References

  1. Levy AT, Cioce V, Sobel ME, et al. Increased expression of the Mr 72,000 type IV collagenase in human colonic adenocarcinoma. Cancer Res 1991;51:439–44.

    Google Scholar 

  2. Kusukawa J, Sasaguri Y, Shima I, Kameyama T, Morimatsu M. Expression of matrix metalloproteinase-2 related to lymph node metastasis of oral squamous cell carcinoma. Am J Clin Pathol 1993;99:8–23.

    Google Scholar 

  3. Matrisian LM, Bowden GT. Stromelysin/transin and tumor progression. Cancer Biol 1990;1:107–15.

    Google Scholar 

  4. Ballin M, Gomez DE, Sinha CC, Thorgeirsson UP. Ras oncogene mediated induction of a 92kDa metalloproteinase; Strong correlation with the malignant phenotype. Biochem Biophys Res Commun 1988;154:832–8.

    Google Scholar 

  5. Yamagata S, Tanaka R, Ito Y, Shimizu S. Gelatinases of murine metastatic tumor cells. Biochem Biophys Res Commun 1989;158:228–34.

    Google Scholar 

  6. Wilhelm SM, Collier IE, Marmer BL, Eisen AZ, Grant GA, Goldberg GI. SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J Biol Chem 1989;264:17213–21.

    Google Scholar 

  7. Yoshimoto M, Itoh F, Yamamoto H, Hinoda Y, Imai K, Yachi A. Expression of MMP-7(PUMP-1) mRNA in human colorectal cancers. Int J Cancer 1993;54:614–8.

    Google Scholar 

  8. Liotta LA, Stetler-Stevenson WG. Tumor invasion and metastasis: an imbalance of positive and negative regulation. Cancer Res 1991;51:5054–9.

    Google Scholar 

  9. Ennis BW, Matrisian LM. Matrix degrading metalloproteinases. J Neurooncol 1994;18:105–9.

    Google Scholar 

  10. Dabbous MK, Torky ME, Haney L, Brinkley SB, Sobhy N. Collagenase activity in rabbit carcinoma: cell source and cell interactions. Int J Cancer 1983;31:357–64.

    Google Scholar 

  11. Baici A, Gyger-Marazzi M, Strauli P. Extracellular cysteine proteinase and collagenase activities as a consequence of tumor-host interaction in the rabbit V2 carcinoma. Invasion Metastasis 1984;4:13–27.

    Google Scholar 

  12. Goslen JB, Eisen AZ, Bauer EA. Stimulation of skin fibroblast collagenase production by a cytokine derived from basal cell carcinomas. J Invest Dermatol 1985;85:161–4.

    Google Scholar 

  13. Basset P, Bellocq JP, Wolf C,et al. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature 1990;348:699–704.

    Google Scholar 

  14. Nuovo GJ, MacConnell PB, Simsir A, Valea F, French DL. Correlation of the in situ detection of polymerase chain reaction-amplified metalloproteinase complementary DNAs and their inhibitors with prognosis in cervical carcinoma. Cancer Res 1995;55:267–75.

    Google Scholar 

  15. Collier IE, Wilhelm SM, Eisen AZ,et al. H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen. J Biol Chem 1988;263:6579–87.

    Google Scholar 

  16. Carmichael DF, Sommer A, Thompson RC,et al. Primary structure and cDNA cloning of human fibroblast collagenase inhibitor. Proc Natl Acad Sci U S A 1986;83:2407–11.

    Google Scholar 

  17. Stetler-Stevenson WG, Brown PD, Onisto M, Levy AT, Liotta LA. Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues. J Biol Chem 1990;265:13, 933–8.

    Google Scholar 

  18. ECL™ 3′-oligolabelling and detection systems. Manual RPN2130/2131. Amersham, UK: Amersham International plc, 1995.

    Google Scholar 

  19. Zeng ZS, Guillem JG. Distinct pattern of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 mRNA expression in human colorectal cancer and liver metastasis. Brit J Cancer 1995;72:575–82.

    Google Scholar 

  20. Nakajima M. Role of matrix metalloproteinases produced by tumor and host cells in tumor metastasis. Exp Med 1994;12:971–9.

    Google Scholar 

  21. Lengyel E, Gum R, Juarez J,et al. Induction of Mr 92,000 type IV collagenase expression in a squamous cell carcinoma cell line by fibroblasts. Cancer Res 1995;55:963–7.

    Google Scholar 

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Masuda, H., Aoki, H. Host expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in normal colon tissue affects metastatic potential of colorectal cancer. Dis Colon Rectum 42, 393–397 (1999). https://doi.org/10.1007/BF02236360

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