[en] Stromelysin-3 (ST3; Basset, P., J.P. Bellocq, C. Wolf, I. Stoll, P. Hutin, J.M. Limacher, O.L. Podhajcer, M.P. Chenard, M.C. Rio, P. Chambon. 1990. Nature. 348:699–704) is a matrix metalloproteinase (MMP) expressed in mesenchymal cells located close to epithelial cells, during physiological and pathological tissue remodeling processes. In human carcinomas, high ST3 levels are associated with a poor clinical outcome, suggesting that ST3 plays a role during malignant processes. In this study we report the ST3 gene inactivation by homologous recombination. Although ST3 null mice (ST3−/−) were fertile and did not exhibit obvious alterations in appearance and behavior, the lack of ST3 altered malignant processes. Thus, the suppression of ST3 results in a decreased 7,12-dimethylbenzanthracene-induced tumorigenesis in ST3−/− mice. Moreover, ST3−/− fibroblasts have lost the capacity to promote implantation of MCF7 human malignant epithelial cells in nude mice (P < 0.008). Finally, we show that this ST3 paracrine function requires extracellular matrix (ECM)-associated growth factors. Altogether, these findings give evidence that ST3 promotes, in a paracrine manner, homing of malignant epithelial cells, a key process for both primary tumors and metastases. Therefore, ST3 represents an appropriate target for specific MMP inhibitor(s) in future therapeutical approaches directed against the stromal compartment of human carcinomas.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Masson, R.
Lefebvre, O.
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
El Fahime, M.
Chenard, M.-P.
Wendling, C.
Kebers, F.
Le Meur, M.
Dierich, A.
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement
Basset, P.
Rio, M. C.
Language :
English
Title :
In vivo evidence that the stromelysin-3 metalloproteinase contributes in a paracrine manner to epithelial cell malignancy
Publication date :
1998
Journal title :
Journal of Cell Biology
ISSN :
0021-9525
eISSN :
1540-8140
Publisher :
Rockefeller University Press, New York, United States - New York
Anglard, P., T. Melot, E. Guérin, G. Thomas, and P. Basset. 1995. Structure and promoter characterization of the human stromelysin-3 gene. J. Biol. Chem. 270:20337-20344.
Basset, P., J.P Bellocq, C. Wolf, I. Stoll, P. Hutin, J.M. Limacher, O.L. Podhajcer, M.P. Chenard, M.C. Rio, and P. Chambon. 1990. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature. 348:699-704.
Basset, P., J.P. Bellocq, O. Lefebvre, A. Noël, M.P. Chenard, C. Wolf, P. Anglard, and M.C. Rio. 1997a. Stromelysin-3: a paradigm for stroma-derived factors implicated in carcinoma progression. Crit. Rev. Oncol.-Hematol. 26:43-53.
Basset, P., A. Okada, M.P. Chenard, R. Kannan, I. Stoll, P. Anglard, J.P. Bellocq, and M.C. Rio. 1997b. Matrix metalloproteinases as stromal effectors of human carcinoma progression: therapeutical implications. Matrix Biol. 15: 534-541.
Beckett, R.P. 1996. Recent advances in the field of matrix metalloproteinase inhibitors. Exp. Opin. Ther. Patents. 6:1305-1315.
Birkedal-Hansen, H. 1995. Proteolytic remodeling of extracellular matrix. Curr. Opin. Cell Biol. 7:728-735.
Boehm, T., J. Folkman, T. Browder, and M.S. O'Reilly, 1997. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature. 390:404-407.
Chenard, M.P., L. O'Siorain, S. Shoring, N. Rouyer, Y. Lutz, C. Wolf, P. Basset, J.P. Bellocq, and M.J. Duffy. 1996. High levels of stromelysin-3 correlate with poor prognosis in patients with breast carcinoma. Int. J. Cancer 69:448-451.
Chomczynski, P., and N. Sacchi. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:156-159.
Cornil, I., D. Theodorescu, S. Man, M. Herlyn, J. Jambrosic, and R.S. Kerbel. 1991. Fibroblast cell interactions with human melanoma cells affect tumor cell growth as a function of tumor progression. Proc. Natl. Acad. Sci. USA. 88:6028-6032.
Coussens, L.M., and Z. Werb. 1996. Matrix metalloproteinases and the development of cancer. Chem. Biol. (Lond). 3:895-904.
Cross, M., and T.M. Dexter. 1991. Growth factors in development, transformation, and tumorigenesis. Cell. 64:271-280.
Cunha, G.R. 1994. Role of mesenchymal-epithelial interactions in normal and abnormal development of the mammary gland and prostate. Cancer. 74(Suppl.):1030-1044.
Dimanche-Boitrel, M.T., L. Vakaet, P. Pujuguet, B. Chauffert, M.S. Martin, A. Hamman, F. Van Roy, M. Mareel, and F. Martin. 1994. In vivo and in vitro invasiveness of a rat colon-cancer cell line maintaining E-cadherin expression: an enhancing role of tumor-associated myofibroblasts. Int. J. Cancer. 56:512-521.
Engel, G., K. Heselmeyer, G. Auer, M. Backdahl, E. Eriksson, and S. Linder. 1994. Correlation between stromelysin-3 mRNA level and outcome of human breast cancer. Int. J. Cancer. 58:830-835.
Gossler, A., T. Doetschman, R. Korn, E. Serfling, and R. Kemler. 1986. Transgenesis by means of blastocyst-derived embryonic stem cell lines. Proc. Natl. Acad. Sci. USA. 83:9065-9069.
Grégoire, M., and B. Lieubeau. 1995. The role of fibroblasts in tumor behavior. Cancer Metast. Rev. 14:339-350.
Hodgson, J. 1995. Remodeling MMPIs. Biotechnology. 13:554-557.
Ip, C. 1996. Mammary tumorigenesis and chemoprevention studies in carcinogen-treated rats. J. Mam. Gland Biol. Neoplasia. 1:37-47.
Itoh, T., T. Ikeda, H. Gomi, S. Nakao, T. Susuki, and S. Itohara. 1997. Unaltered secretion of β-amyloid precursor protein in gelatinase A (matrix metalloproteinase 2)-deficient mice. J. Biol. Chem. 272:22389-22392.
Kerbel, R.S. 1997. A cancer therapy resistant to resistance. Nature. 390:335-336.
Lefebvre, O., C. Wolf, J.M. Limacher, P. Hutin, C. Wendling, M. LeMeur, P. Basset, and M.C. Rio. 1992. The breast cancer-associated stromelysin-3 gene is expressed during mouse mammary gland apoptosis. J. Cell Biol. 119:997-1002.
Lefebvre, O., C. Régnier, M.C. Chenard, C. Wendling, P. Chambon, P. Basset, and M.C. Rio. 1995. Developmental expression of mouse stromelysin-3 mRNA. Development. 121:947-955.
Loo, D., C. Rawson, T. Ernst, S. Shirahata, and D. Barnes. 1990. Primary and multipassage culture of mouse embryo cells in serum-containing and serum-free media. In Cell Growth and Division. R. Baserga, editor. IRL Press, Oxford, UK. 17-35.
Lufkin, T., A. Dierich, M. LeMeur, M. Mark, and P. Chambon. 1991. Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression. Cell. 65:1105-1119.
MacDougall, J.R., and L.M. Matrisian. 1995. Contributions of tumor and stromal matrix metalloproteinases to tumor progression, invasion and metastasis. Cancer Metast. Rev. 14:351-362.
Maquoi, E., M. Polette, B. Nawrocki, P. Bischof, A. Noël, A. Pintiaux, M. Santavicca, J.P. Schaaps, P. Birembaut, and J.M. Foidart. 1997. Expression of stromelysin-3 in the human placenta and placenta bed. Placenta. 18:277-285.
Masiakowski, P., R. Breathnach, J. Block, F. Gannon, A. Krust, and P. Chambon. 1982. Cloning of cDNA sequences of hormone-regulated genes from the MCF7 human breast cancer cell line. Nucleic Acids Res. 10:7895-7903.
Muller, D., C. Wolf, J. Abecassis, R. Millon, A. Engelmann, G. Bronner, N. Rouyer, M.C. Rio, M. Eber, G. Methlin et al. 1993. Increased stromelysin-3 gene expression is associated with increased local invasiveness in head and neck squamous carcinomas. Cancer Res. 53:165-169.
Noël, A., M.C. De Pauw-Gillet, G. Purnell, B. Nusgens, C.M. Lapiere, and J.M. Foidart. 1993. Enhancement tumorigenicity of human breast adenocarcinoma cells in nude mice by matrigel and fibroblasts. Br. J. Cancer. 68:909-915.
Noël, A., M. Santavicca, I. Stoll, C. L'Hoir, A. Staub, G. Murphy, M.C. Rio, and P. Basset. 1995. Identification of structural determinants controlling human and mouse stromelysin-3 proteolytic activities. J. Biol. Chem. 270: 22866-22872.
Noël, A., O. Lefebvre, E. Maquoi, L. Vanhoorde, M.P. Chenard, M. Mareel, J.M. Foidart, P. Basset, and M.C. Rio. 1996. Stromelysin-3 expression promotes tumor take in nude mice. J. Clin. Invest. 97:1924-1930.
Okada, A., S. Saez, Y. Misumi, and P. Basset. 1997. Rat stromelysin-3: cDNA cloning from healing skin wound, activation by furin and expression in rat tissues. Gene. 185:187-193.
Patterton, D., W. Pär Haves, and Y.B. Shi. 1995. Transcriptional activation of the matrix metalloproteinase gene stromelysin-3 coincides with thyroid hormone-induced cell death during frog metamorphosis. Dev. Biol. 167:252-262.
Pei, D., G. Majmudar, and S.J. Weiss. 1994. Hydrolytic inactivation of a breast carcinoma cell-derived serpin by human stromelysin-3. J. Biol. Chem. 269: 25849-25855.
Pei, D., and S.J. Weiss. 1995. Furin-dependent intracellular activation of the human stromelysin-3 zymogen. Nature. 375:244-247.
Porte, H., E. Chastre, S. Prevot, B. Nordlinger, S. Empereur, P. Basset, P. Chambon, and C. Gespach. 1995. Neoplastic progression of human colorectal cancer is associated with overexpression of the stromelysin-3 and BM-40/SPARC genes. Int. J. Cancer. 64:70-75.
Rio, M.C., O. Lefebvre, M. Santavicca, A. Noël, M.P. Chenard, P. Anglard, J.A. Byrne, A. Okada, C.H. Régnier, R. Masson et al. 1996. Stromelysin-3 in the biology of the normal and neoplastic mammary gland. J. Mam. Gland Biol. Neoplasia. 1:231-240.
Rodgers, W.H., L.M. Matrisian, L.C. Giudice, B. Dsupin, P. Cannon, C. Sviteck, F. Gorstein, and K.G. Osteen. 1994. Patterns of matrix metalloproteinase expression in cycling endometrium imply differential functions and regulation by steroid hormones. J. Clin. Invest. 94:946-953.
Rouyer, N., C. Wolf, M.P. Chenard, M.C. Rio, P. Chambon, J.P. Bellocq, and P. Basset. 1994. Stromelysin-3 gene expression in human cancer: an overview. Invasion Metastasis. 14:269-275.
Ruoslahti, E., and Y. Yamaguchi. 1991. Proteoglycans as modulators of growth factor activities. Cell. 289:867-869.
Santavicca, M., A. Noël, M.P. Chenard, Y. Lutz, I. Stoll, J.P. Segain, N. Rouyer, M.C. Rio, C. Wolf, J.P. Bellocq, and P. Basset. 1995. Characterization of monoclonal antibodies against stromelysin-3 and their use to evaluate stromelysin-3 levels in breast carcinoma by semi-quantitative immunohistochemistry. Int. J. Cancer. 64:336-341.
Stetler-Stevenson, W.G., R. Hewitt, and M. Corcoran. 1996. Matrix metalloproteinases and tumor invasion: from correlation and causality to the clinic. Semin. Cancer Biol. 7:147-154.
Sukumar, S. 1990. An experimental analysis of cancer: role of ras oncogene in multistep carcinogenesis. Cancer Cells. 2:199-204.
Tagughi, O., S.D. Michael, and Y. Nishizuka. 1988. Rapid induction of ovarian granulosa cell tumors by 7,12-dimethylbenz(a)anthracene in neonatally estrogenized mice. Cancer Res. 48:425-429.
Taub, M., Y. Wang, T.M. Szczesny, and H.K. Kleinman. 1990. Epidermal growth factor or transforming growth factor a is required for kidney tubulogenesis in matrigel cultures in serum-free medium. Proc. Natl. Acad. Sci. USA. 87:4002-4006.
Wang, Z., and D. Brown. 1993. Thyroid hormone-induced gene expression program for amphibian tail resorption. J. Biol. Chem. 268:16270-16278.
Wilson, C.L., K.J. Heppner, P.A. Labosky, B.L.M. Hogan, and L. Matrisian. 1997. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc. Natl. Acad. Sci. USA. 94:1402-1407.
Wolf, C., M.P. Chenard, P. Durand de Grossouvre, J.P. Bellocq, P. Chambon, and P. Basset. 1992. Breast-cancer-associated stromelysin-3 gene is expressed in basal cell carcinoma and during cutaneous wound healing. J. Invest. Dermatol. 99:870-872.
