Skip to main content
Log in

Expression of the stromelysin-3 gene in fibroblastic cells of invasive carcinomas of the breast and other human tissues: a review

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

Stromelysin-3 (ST3) is a putative new matrix metalloproteinase (MMP) which may play a role in the progression of human carcinomas, and exhibits unique structural and functional characteristics among the MMP family. The ST3 gene, which is generally not expressed at significant levels in benign breast tumors, has been found to be expressed in all invasive breast carcinomas tested so far. The gene is also expressed in somein situ breast carcinomas, which have a higher probability to become invasive. ST3 RNA and protein are specifically found in fibroblastic cells immediately surrounding the neoplastic cells, both in invasive andin situ breast carcinomas. The same expression pattern is observed in other types of human carcinomas, and the highest ST3 RNA levels are observed in tumors that exhibit high local invasiveness. The ST3 gene is also expressed in fibroblastic cells during the inflammatory phase of wound healing, which suggests that ST3 gene expression in stromal fibroblasts may be under the control of factors produced by inflammatory cells during wound healing, and by cancer cells during carcinoma progression. ST3 may thus represent a stroma-derived factor necessary for the progression of epithelial malignancies, and its manipulation may possibly be used to develop new anti-cancer agents.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Clark WH: Tumor progression and the nature of cancer. Br J Cancer 64:631–644, 1991

    PubMed  Google Scholar 

  2. Klein G, Klein E: Evolution of tumours and the impact of molecular oncology. Nature 315:190–195, 1985

    PubMed  Google Scholar 

  3. Hart IR, Easty D: Tumor cell progression and differentiation in metastasis. Sem Cancer Biol 2:87–95, 1991

    Google Scholar 

  4. Basset P, Bellocq JP, Wolf C, Stoll I, Hutin P, Limacher JM, Podhajcer OL, Chenard MP, Rio MC, Chambon P: A novel metalloproteinase gene specifically expressed in stomal cells of breast carcinomas. Nature 348:699–704, 1990

    PubMed  Google Scholar 

  5. Matrisian LM: The matrix-degrading metalloproteinases. BioEssays 14:455–463, 1992.

    PubMed  Google Scholar 

  6. Nakajima M, Chop AM: Tumor invasion and extracellular matrix degradative enzymes: regulation of activity by organ factors. Sem Cancer Biol 2:115–127, 1991

    Google Scholar 

  7. Liotta LA, Stetler-Stevenson WG: Invasion and metastasis: an imbalance of positive and negative regulation. Cancer Res 51:5054s-5059s, 1991

    PubMed  Google Scholar 

  8. Nicolson GL: Tumor and host molecules important in the organ preference of metastasis. Sem Cancer Biol 2:143–154, 1991

    Google Scholar 

  9. Whitham SE, Murphy G, Angel P, Rahmsdorf HJ, Smith BJ, Lyons A, Harris TJR, Reynolds JJ, Herrlich P: Comparison of human stromelysin and collagenase by cloning and sequence analysis. Biochem J 240:913–916, 1986

    PubMed  Google Scholar 

  10. Muller D, Quantin B, Gesnel MC, Millon-Collard R, Abecassis J, Breathnach R: The collagenase gene family in humans consists of at least four members. Biochem J 253:187–192, 1988

    PubMed  Google Scholar 

  11. Levy A, Zucman J, DeLattre O, Mattei MG, Rio MC, Basset P: Assignment of the human stromelysin-3 (STMY3) gene to the q11.2 region of chromosome 22. Genomics 13:881–883, 1992

    PubMed  Google Scholar 

  12. Spurr NK, Gough AC, Gosden J, Rout D, Porteous DJ, Van Heyningen V, Docherty AJP: Restriction fragment length polymorphism analysis and assignment of the metalloproteinases stromelysin and collagenase to the long arm of chromosome 11. Genomics 2:119–127, 1988

    PubMed  Google Scholar 

  13. Sirum KL, Brinckerhoff CE: Cloning of the genes for human stromelysin and stromelysin 2: Differential expression in rheumatoid synovial fibroblasts. Biochemistry 28:8691–8698, 1989

    PubMed  Google Scholar 

  14. Huhtala P, Eddy RL, Fan YS, Byers MG, Shows TB, Tryggvason K: Completion of the primary structure of the human type IV collagenase preproenzyme and assignment of the gene (CLG4) to the q21 region of chromosome 16. Genomics 6:554–559, 1990

    PubMed  Google Scholar 

  15. Collier IE, Bruns GAP, Goldberg GI, Gerhard DS: On the structure and chromosome location of the 72- and 92-kDa human type IV collagenase genes. Genomics 9:429–434, 1991

    PubMed  Google Scholar 

  16. Shapiro SD, Griffin GL, Gilbert DJ, Jenkins NA, Copeland NG, Welgus HG, Senior RM, Ley TJ: Molecular cloning, chromosomal localization, and bacterial expression of a murine macrophage metalloelastase. J Biol Chem 267:4664–4671, 1991

    Google Scholar 

  17. Murphy GJP, Murphy G, Reynolds JJ: The origin of matrix metalloproteinases and their familial relationships. FEBS Lett 289:4–7, 1991

    PubMed  Google Scholar 

  18. Lefebvre O, Wolf C, Limacher J, Hutin P, Wendling C, LeMeur M, Basset P, Rio C: The breast cancer-associated stromelysin-3 gene is expressed during mouse mammary gland apoptosis. J Cell Biol, in press, 1992

  19. Hecht PM, Anderson KV: Extracellular proteases and embryonic pattern formation. Trends Cell Biol 2:197–202, 1992

    PubMed  Google Scholar 

  20. Monteagudo C, Merino MJ, San-Juan J, Liotta LA, Stetler-Stevenson WG: Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. Am J Pathol 136:585–592, 1990

    PubMed  Google Scholar 

  21. Harris JR, Lippman ME, Veronesi U, Willett W: Breast cancer. N Engl J Med 327:390–398, 1992.

    PubMed  Google Scholar 

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

  23. Jacobs GH, Rippey JJ, Altini M: Prediction of aggressive behavior in basal cell carcinoma. Cancer 49:533–537, 1982

    PubMed  Google Scholar 

  24. Wolf C, Chenard MP, Durand de Grossouvre P, Bellocq JP, Chambon P, Basset P: The breast cancer-associated stromelysin-3 gene is expressed in basal cell carcinoma and during cutaneous wound healing. J Invest Dermatol, in press, Dec 1992

  25. Liotta LA, Nageswara Rao C, Wewer UM: Biochemical interactions of tumor cells with the basement membrane. Ann Rev Biochem 55:1037–1057, 1986

    PubMed  Google Scholar 

  26. Blake Goslen J, Bauer EA: Basal cell carcinoma and collagenase. J Dermatol Surg Oncol 12:812–817, 1986

    PubMed  Google Scholar 

  27. Polette M, Clavel C, Muller D, Abecassis J, Binninger I, Birembaut P: Detection of mRNAs encoding collagenase I and stromelysin 2 in carcinomas of the head and neck byin situ hybridization. Invasion Metastasis 11:76–83, 1991

    PubMed  Google Scholar 

  28. Pyke C, Ralfkiaer E, Huhtala P, Hurskainen T, Danø K, Tryggvason K: Localization of messenger RNA for Mr 72,000 and 92,000 type IV collagenases in human skin cancers byin situ hybridization. Cancer Res 52:1336–1341, 1992

    PubMed  Google Scholar 

  29. Grøndahl-Hansen J, Ralfkiaer E, Kirkeby LT, Kristensen P, Lund LR, Danø K: Localization of urokinase-type plasminogen activator in stromal cells in adenocarcinomas of the colon in humans. Am J Pathol 138:111–117, 1991

    PubMed  Google Scholar 

  30. Pyke C, Kristensen P, Ralfkiaer E, Grøndahl-Hansen J, Eriksen J, Blasi F, Danø K: Urokinase-type plasminogen activator is expressed in stromal cells and its receptor in cancer cells at invasive foci in human colon adenocarcinomas. Am J Pathol 138:1059–1067, 1991

    PubMed  Google Scholar 

  31. Wicha MM, Liotta LA, Vonderhaar BC, Kidwell WR: Effects of inhibition of basement membrane collagen deposition on rat mammary gland development. Devel Biol 80:253–266, 1980

    Google Scholar 

  32. Streuli CH, Bailey N, Bissell MJ: Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity. J Cell Biol 115:1383–1395, 1991

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  34. Talhouk RS, Chin JR, Unemori EN, Werb Z, Bissell MJ: Proteinases of the mammary gland: developmental regulation in vivo and vectorial secretion in culture. Development 112:439–449, 1991

    PubMed  Google Scholar 

  35. Dvorak HF: Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650–1659, 1986

    PubMed  Google Scholar 

  36. Van den Hooff A: Stromal involvement in malignant growth. Adv Cancer Res 50:159–196, 1988

    PubMed  Google Scholar 

  37. Van den Hooff A: The role of stromal cells in tumor metastasis: a new link. Cancer Cells 3:186–187, 1991

    PubMed  Google Scholar 

  38. Jänicke F, Schmitt M, Ulm K, Gössner W, Graeff H: The urokinase-type plasminogen activator (uPA) antigen is related to early relapse in breast cancer. Lancet ii:1049, 1989

    Google Scholar 

  39. Jänicke F, Schmitt M, Hafter R, Hollrieder A, Babic R, Ulm K, Gössner W, Graeff H: The urokinase-type plasminogen activator (uPA) is a potent indicator of early relapse in breast cancer. Fibrinolysis 4:1–10, 1990

    Google Scholar 

  40. Ingber DE: Extracellular matrix as a solid-state regulator in angiogenesis: identification of new targets for anti-cancer therapy. Sem Cancer Biol 3:57–63, 1992

    Google Scholar 

  41. Folkman J, Shing Y: Angiogenesis. J Biol Chem 267:10931–10934, 1992

    PubMed  Google Scholar 

  42. Collier IE, Wilhelm SM, Eisen AZ, Marmer BL, Grant GA, Seltzer JL, Kronberger A, He C, Bauer EA, Goldberg GI: H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen. J Biol Chem 263:6579–6587, 1988

    PubMed  Google Scholar 

  43. Rio MC, Bellocq JP, Gairard B, Rasmussen UB, Krust A, Koehl C, Calderoli H, Schiff V, Renaud R, Chambon P: Specific expression of the pS2 gene in subclasses of breast cancers in comparison with expression of the estrogen and progesterone receptors and the oncogene ERBB2. Proc Natl Acad Sci USA 84:9243–9247, 1987

    PubMed  Google Scholar 

  44. Nagai M, Hiramatsu R, Kaneda T, Hayasuke N, Arimura H, Nishida M, Suyama T: Molecular cloning of cDNA coding for human preprourokinase. Gene 36:183–188, 1985

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Basset, P., Wolf, C. & Chambon, P. Expression of the stromelysin-3 gene in fibroblastic cells of invasive carcinomas of the breast and other human tissues: a review. Breast Cancer Res Tr 24, 185–193 (1993). https://doi.org/10.1007/BF01833259

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01833259

Key words

Navigation