Skip to main content
SpringerLink
Log in

Stromelysin-3 in the biology of the normal and neoplastic mammary gland

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Stromelysin-3 (ST3) is an extracellular proteinase predominantly expressed in fibroblasts. The particular structural features andin vitro functions of this molecule suggest it could be the first member of a new subgroup of the matrix metalloproteinase family. ST3 is transiently expressed during mammary gland post-weaning involution, embryonic implantation, various organogeneses, and during amphibian metamorphosis. Moreover, ST3 is expressed in a panel of human invasive carcinomas including breast, colon, and head and neck carcinomas. Almost all ST3-expressing tissues show intense extracellular matrix remodeling activities including the loss of basement membrane integrity. Thus, either directly, or indirectly in association with other proteinases, ST3 might be involved in tissue remodeling processes occurring in both physiological and pathological processes.In vitro andin vivo studies using malignant cells stably transfected in such a way as to modulate their ST3 expression levels indicate that ST3 modifies neither cell proliferation nor invasive properties, but rather favors tumor cell survival in host tissues. This hypothesis is consistent with clinical data showing that ST3 expression could be predictive of tumor progression leading to metastases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ECM:

Extracellular matrix

MMPs:

matrix metalloproteinases

ST1:

stromelysin-1

ST2:

stromelysin-2

ST3:

stromelysin-3

TIMPs:

tissue inhibitor of metalloproteinases

tPA:

tissue type plasminogen activator

uPA:

urokinase type plasminogen activator

References

  1. B. Vogelstein and K. Kinzler (1993). The multistep nature of cancer.Trends Genet. 9:138–141.

    PubMed  Google Scholar 

  2. H. F. Dvorak (1986). Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing.New Engl. J. Med. 315:1650–1659.

    PubMed  Google Scholar 

  3. A. van den Hoff (1988). Stromal involvement in malignant growth.Adv. Cancer Res. 50:159–196.

    PubMed  Google Scholar 

  4. W. G. Stetler-Stevenson, S. Aznavoorian, and L. A. Liotta (1993). Tumor cell interactions with the extracellular matrix during invasion and metastasis.Annu. Rev. Cell Biol. 9:541–573.

    PubMed  Google Scholar 

  5. C. Lin and M. Bissel (1993). Multifaceted regulation of cell differentiation by extracellular matrix.FASEB J. 7:737–743.

    PubMed  Google Scholar 

  6. C. Birchmeier and W. Birchmeier (1993). Molecular aspects of mesenchymal-epithelial interactions.Annu. Rev. Cell Biol. 9:511–540.

    PubMed  Google Scholar 

  7. L. R. Bernstein and L. A. Liotta (1994). Molecular mediators of interactions with extracellular matrix components in metastasis and angiogenesis.Curr. Opin. Oncol. 6:106–113.

    PubMed  Google Scholar 

  8. I. J. Fidler and L. M. Ellis (1994). The implications of angiogenesis for the biology and therapy of cancer metastasis.Cell 79:185–188.

    PubMed  Google Scholar 

  9. J. Folkman (1995). Angiogenesis in cancer, vascular, rheumatoid, and other disease.Nature Med. 1:27–31.

    PubMed  Google Scholar 

  10. L. M. Matrisian (1992). The matrix-degrading metalloproteinases.BioEssays 14:455–463.

    PubMed  Google Scholar 

  11. J. R. Woessner (1995). The family of matrix metalloproteinases. In R. Greenwald and L. Golub (eds.),Inhibition of Matrix Metalloproteinases; Therapeutic Potential. Annals, N.Y. Acad. Sciences, New York, pp. 11–21.

    Google Scholar 

  12. H. Birkedal-Hansen (1995). Proteolytic remodeling of extracellular matrix.Curr. Opin. Cell Biol. 7:728–735.

    PubMed  Google Scholar 

  13. P. Mignatti and D. B. Rifkin (1993). Biology and biochemistry of proteinases in tumor invasion.Physiol. Rev. 73:161–195.

    PubMed  Google Scholar 

  14. P. Basset, 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.

    PubMed  Google Scholar 

  15. D. Pei and S. Weiss (1995). Furin-dependent intracellular activation of the human stromelysin-3 zymogen.Nature 375:244–247.

    PubMed  Google Scholar 

  16. H. Sato, T. Takino, Y. Okada, J. Cao, A. Shinagawa, E. Yamamoto, and M. Seiki (1994). A matrix metalloproteinase expressed on the surface of invasive tumour cells.Nature 230:61–65.

    Google Scholar 

  17. A. Okada, J. P. Bellocq, N. Rouyer, M. P. Chenard, M. C. Rio, P. Chambon, and P. Basset (1995). Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head, and neck carcinomas.Proc. Natl. Acad. Sci. U.S.A. 92:2730–2734.

    PubMed  Google Scholar 

  18. D. Pei, 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.

    PubMed  Google Scholar 

  19. A. Noël, 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.

    PubMed  Google Scholar 

  20. G. Murphy, J. P. Segain, M. O'Shea, M. Cockett, C. Ioannou, O. Lefebvre, P. Chambon, and P. Basset (1993). The 28kd N-terminal domain of mouse Stromelysin-3 has the general properties of a weak stromelysin-like metalloproteinase.J. Biol. Chem. 268:15435–15441.

    PubMed  Google Scholar 

  21. P. Anglard, 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.

    PubMed  Google Scholar 

  22. C. Wolf, 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.

    PubMed  Google Scholar 

  23. A. Okada (unpublished).

  24. C. Wolf, N. Rouyer, Y. Lutz, C. Adida, M. Loriot, J. P. Bellocq, P. Chambon, and P. Basset (1993). Stromelysin-3 belongs to a subgroup of proteinases expressed in breast carcinoma fibroblastic cells and possibly implicated in tumor progression.Proc. Natl. Acad. Sci. U.S.A. 90:1843–1847.

    PubMed  Google Scholar 

  25. J. Byrne, C. Tomasetto, N. Rouyer, J. P. Bellocq, M. C. Rio, and P. Basset (1995). The tissue inhibitor of metalloproteinase-3 gene in breast carcinoma: identification of multiple polyadenylation sites and a stromal pattern of expression.Mol. Med. 1:418–427.

    PubMed  Google Scholar 

  26. N. Rouyer, C. Wolf, M. P. Chenard, M. C. Rio, P. Chambon, J. P. Bellocq, and P. Basset (1994–1995). Stromelysin-3 gene expression in human cancer: an overview.Invasion/Metast.14:269–275.

    Google Scholar 

  27. D. Muller, C. Wolf, J. Abecassis, R. Millon, A. Engelmann, G. Bronner, N. Rouyer, M. C. Rio, M. Eber, G. Methlin, P. Chambon, and P. Basset (1993). Increased stromelysin-3 gene expression is associated with increased local invasiveness in head and neck squamous cell carcinomas.Cancer Res. 53:165–169.

    PubMed  Google Scholar 

  28. H. Porte, 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 over-expression of the stromelysin-3 and BM-40/SPARC genes.Int. J. Cancer 64:70–75.

    PubMed  Google Scholar 

  29. G. Engel, 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.

    PubMed  Google Scholar 

  30. E. Hähnel, J. Harvey, R. Joyce, P. Robbins, G. Sterrett, and R. Hähnel (1993). Stromelysin-3 expression in breast cancer biopsies: clinicopathological correlations.Int. J. Cancer 55:771–774.

    PubMed  Google Scholar 

  31. H. Sutherland, G. Dougherty, and S. Dedhar (1990). Developmental biology and oncology: two sides to the same coin?New Biologist. 2:970–973.

    PubMed  Google Scholar 

  32. A. P. Sappino, J. Huarte, D. Belin, and J. D. Vassalli (1989). Plasminogen activators in tissue remodeling and invasion: mRNA localization in mouse ovaries and implanting embryos.J. Cell Biol. 109:2471–2479.

    PubMed  Google Scholar 

  33. O. Lefebvre, C. Wolf, J. M. Limacher, P. Hutin, C. Wendling, M. LeMeur, P. Basset, and M. C. Rio (1992). The breast cancerassociated stromelysin-3 gene is expressed during mouse mammary gland apoptosis.J. Cell Biol. 119:997–1002.

    PubMed  Google Scholar 

  34. O. Lefebvre, C. H. Régnier, M. P. Chenard, C. Wendling, P. Chambon, P. Basset, and M. C. Rio (1995). Developmental expression of mouse stromelysin-3 mRNA.Development 121:947–955.

    PubMed  Google Scholar 

  35. D. Patterton, W. Pär Hayes, and Y. B. Shi (1995). Transcriptional activation of the matrix metalloproteinase gene stromely-sin-3 coincides with thyroid hormone-induced cell death during frog metamorphosis.Dev. Biol. 167:252–262.

    PubMed  Google Scholar 

  36. M. M. Wicha, L. A. Liotta, B. C. Vonderhaar, and W. R. Kidwell (1980). Effects of inhibition of basement membrane collagen deposition on rat mammary gland development.Dev. Biol. 80:253–266.

    PubMed  Google Scholar 

  37. A. Martinez-Hernandez, L. M. Fink, and G. Barry Pierce (1976). Removal of basement membrane in the involuting breast.Lab. Invest. 34:455–462.

    PubMed  Google Scholar 

  38. R. S. Talhouk, J. R. Chin, E. N. Unemori, Z. Werb, and M. J. Bissell (1991). Proteinases of the mammary gland: developmental regulationin vivo and vectorial secretion in culture.Development 112:439–449.

    PubMed  Google Scholar 

  39. L. D. Ossowski, L. D. Biegel, and E. Reich (1979). Mammary plasminogen activator. Correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue.Cell 16:929–940.

    PubMed  Google Scholar 

  40. F. Li, R. Strange, R. Friis, V. Djonov, H-J Altermatt, S. Saurer, H. Niemann, and A. C. Andres (1994). Expression of stromely-sin-1 and TIMP1 in the involuting mammary gland and early invasive tumors of the mouse.Int. J. Cancer 59:560–568.

    PubMed  Google Scholar 

  41. E. Ruoslahti and Y. Yamaguchi (1991). Proteoglycans as modulators of growth factor activities.Cell 289:867–869.

    Google Scholar 

  42. S. Strickland and W. G. Richards (1992). Invasion of the trophoblast.Cell 71:355–357.

    PubMed  Google Scholar 

  43. P. Reponen, I. Leivo, C. Sahlberg, S. Apte, B. Olsen, I. Thesleff, and K. Tryggvason (1995). 92-kDA type IV collagenase and TIMP-3, but not 72-kDa type IV collagenase or TIMP-1 or TIMP-2, are highly expressed during mouse embryon implantation.Dev. Dynamics 202:388–396.

    Google Scholar 

  44. J-P. Bellocq (unpublished).

  45. Z. Wang and D. D. Brown (1993). Thyroid hormone-induced gene expression program for amphibian tail resorption.J. Biol. Chem. 268:16270–16278.

    PubMed  Google Scholar 

  46. G. S. Stein, J. B. Lian, and T. A. Owen (1990). Bone cell differentiation: a functionally coupled relationship between expression of cell-growth and tissue-specific genes.Curr. Opin. Cell Biol. 2:1018–1027.

    PubMed  Google Scholar 

  47. M. Meikle, S. Bord, R. Hembry, J. Compston, P. Croucher, and J. Reynolds (1992). Human osteoblasts in culture synthesize collagenase and other matrix metalloproteases in response to osteotropic hormones and cytokines.J. Cell Sci. 103:1093–1099.

    PubMed  Google Scholar 

  48. S. Nomura, B. Hogan, A. Wills, J. Heath, and D. Edwards (1989). Developmental expression of tissue inhibitor of metalloproteinase (TIMP) RNA.Development 105:575–583

    PubMed  Google Scholar 

  49. R. Pittman and H. Buettner (1989). Degradation of extracellular matrix by neuronal proteases.Dev. Neurosci. 11:361–375.

    PubMed  Google Scholar 

  50. W. C. Powell, J. D. Knox, M. Navre, T. M. Grogan, J. Kittelson, R. B. Nagle, and G. T. Bowden (1993). Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice.Cancer Res. 53:417–422.

    PubMed  Google Scholar 

  51. H. Yamamoto, F. Itoh, Y. Hinoda, and K. Imai (1995). Suppression of matrilysin inhibits colon cancer cell invasionin vitro.Int. J. Cancer 61:218–222.

    PubMed  Google Scholar 

  52. A. J. P. Docherty, M. I. Cockett, M. L. Birch, S. Chander, N. Willmott, J. P. O'Connell, T. Crabbe, A. Mountain, J. R. Morphy, T. A. Millican, N. R. A. Beeley, G. Murphy, I. R. Hart, G. Stamp, and V. Mahadevan (1994). Gelatinase inhibitors for treatment of cancer.Clin. Exp. Metast. 12:25.

    Google Scholar 

  53. E. J. Bernhard, S. Gruber, and R. J. Muschel (1994). Direct evidence linking expression of matrix metalloproteinase 9 (92 kDa gelatinase/collagenase) to the metastatic phenotype in transformed rat embryo cells.Proc. Natl. Acad. Sci. U.S.A. 91:4293–4297.

    PubMed  Google Scholar 

  54. R. Khokha, P. Waterhouse, S. Yagel, P. K. Lala, C. M. Overall, G. Norton, and D. Denhardt (1989). Antisense RNA induced reduction in murine TIMP levels confers oncogenicity on Swiss 3T3 cells.Science 243:947–950.

    PubMed  Google Scholar 

  55. Y. A. DeClerck, N. Perez, H. Shimada, T. C. Boone, K. E. Langley, and S. M. Taylor (1992). Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases.Cancer Res. 52:701–708.

    PubMed  Google Scholar 

  56. C. J. Sympson, R. S. Talhouk, C. M. Alexander, J. R. Chin, S. M. Cliff, M. J. Bissel, and Z. Werb (1994). Targeted expression of ST1 in mammary gland provides evidence for a role of proteinases in branching morphogenesis and the requirement for an intact basement membrane for tissue-specific gene expression.J. Cell Biol. 125:681–693.

    PubMed  Google Scholar 

  57. J. P. Witty, T. Lempka, J. Coffey, Jr., and L. M. Matrisian (1995). Decreased tumor formation in 7,12-dimethylbenzanthracenetreated stromelysin-1 transgenic mice is associated with alterations in mammary epithelial cell apoptosis.Cancer Res. 55:1401–1406.

    PubMed  Google Scholar 

  58. J. Hodgson (1995). Remodeling MMPIs.Biotechnology 13:554–557.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale U184/Université Louis Pasteur, BP 163, 67404, Illkirch Cedex, C.U. de Strasbourg, France

    Marie-Christine Rio, Olivier Lefebvre, Maria Santavicca, Agnès Noël, Patrick Anglard, Jennifer A. Byrne, Akiko Okada, Catherine H. Régnier, Régis Masson & Paul Basset

  2. Service d'Anatomie Pathologique Générale, Centre Hospitalier Universitaire de Hautepierre, 67098, Strasbourg Cedex, France

    Marie-Pierre Chenard & Jean-Pierre Bellocq

Authors
  1. Marie-Christine Rio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olivier Lefebvre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Santavicca
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Agnès Noël
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marie-Pierre Chenard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Patrick Anglard
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jennifer A. Byrne
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Akiko Okada
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Catherine H. Régnier
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Régis Masson
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jean-Pierre Bellocq
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Paul Basset
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rio, MC., Lefebvre, O., Santavicca, M. et al. Stromelysin-3 in the biology of the normal and neoplastic mammary gland. J Mammary Gland Biol Neoplasia 1, 231–240 (1996). https://doi.org/10.1007/BF02013646

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02013646

Key words

Search

Navigation