Advertisement

Virchows Archiv

, Volume 428, Issue 1, pp 29–35 | Cite as

MT-MMP expression and localisation in human lung and breast cancers

  • M. Polette
  • B. Nawrocki
  • J. -M. Tournier
  • P. Birembaut
  • C. Gilles
  • H. Sato
  • M. Seiki
Original Articles

Abstract

Thirteen primary pulmonary squamous cell carcinomas, 4 specimens of normal lung from around tumours, 4 benign proliferations of the mammary gland and 16 breast carcinomas were analysed by in situ hybridisation, Northern blot and immunohistochemistry for the expression of a recently described metalloproteinase (MMP), the MT-MMP (membrane-type matrix metalloproteinase). This MT-MMP can activate gelatinase A, involved in the degradation of basement membranes. In situ hybridisation revealed MT-MMP transcripts distributed in both tumour and stromal cells in squamous cell lung cancers, whereas these mRNAs were principally detected in stromal cells in close contact to tumour clusters in breast carcinomas and in lung adenocarcinomas. Northern blot analysis showed a parallel expression of MT-MMP and gelatinase A transcripts in both lung and breast cancers. Immunohistochemistry displayed a more extensive distribution of MT-MMP in pulmonary and mammary carcinomas with numerous labelled preinvasive and infiltrating cancer cells and stromal cells near the tumour cells. The large degree of expression of MT-MMP in these cancers indicates a potential role of this enzyme in tumour progression. The finding of MT-MMP transcripts in stromal cells in the vicinity of lung and breast tumour cells emphasises the cooperation between these cells and cancer cells for the expression of MT-MMP and in tumour invasion in vivo.

Key words

Metalloproteinases Breast cancer Lung cancer Invasion 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Azzam HS, Thompson EW (1992) Collagen induced activation of the 72 kDa type IV collagenase in human fibroblasts and a carcinosarcoma-derived human breast cancer cell line. Cancer Res 25:4540–4544Google Scholar
  2. 2.
    Azzam HS, Arand GA, Lippman ME, Thompson EW (1993) MMP-2 activation potential associates with metastatic progression in human breast cancer cell lines, and is independent of MMP-2 production. J Natl Cancer Inst 85:1758–1764Google Scholar
  3. 3.
    Basset P, Bellocq JP, Wolf C, Stoll I, Limacher JM, Podjahcer OL, Chenard MP, Rio MC, Chambon P (1990) A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature 348:699–704Google Scholar
  4. 4.
    Brown PD, Kleiner DE, Unsworth EJ, Stetler-Stevenson WG (1993) Cellular activation of the 72 kDa type IV collagenase/TIMP2 complex. Kidney Int 43:163–170Google Scholar
  5. 5.
    Clavel C, Polette M, Doco M, Binninger I, Birembaut I (1992) Immunolocalization of matrix metalloproteinases and their tissues inhibitor in human mammary pathology. Bull Cancer (Paris) 79:261–270Google Scholar
  6. 6.
    Daidone MG, Silvestrini R, D'Errico A, Di Fronzo G, Benini E, Mancini AM, Garbisa S, Liotta LA, Grigioni WF (1991) Laminin receptors, collagenase IV and prognosis in node-negative breast cancers. Int J Cancer 48:529–532Google Scholar
  7. 7.
    Davies B, Miles DW, Happerfield LC, Naylor MS, Bobrow LG, Rubens RD, Balkwill FR (1993) Activity of type IV collagenases in benign and malignant breast disease. Br J Cancer 67:1126–1131Google Scholar
  8. 8.
    D'Errico A, Garbisa S, Liotta LA, Castronovo V, Stetler-Stevenson WG, Grigioni WF (1991) Augmentation of type IV collagenase, laminin receptor and KI67 proliferation antigen associated with human colon, gastric and breast carcinoma progression. Mod Pathol 4:239–246Google Scholar
  9. 9.
    Emonard H, Remacle A, Noel A, Grimaud JA, Stetler-Stevenson WG, Foidart JM (1992) Tumor cell surface associated binding site for the Mr 72,000 type IV collagenase. Cancer Res 52:5845–5848Google Scholar
  10. 10.
    Gilles C, Polette M, Piette J, Birembaut P, Foidart JM (1994) Epithelial-to-mesenchymal transition in HPV-33-transfected cervical keratinocytes in associated with increased invasiveness and expression of gelatinase A. Int J Cancer 59:661–666Google Scholar
  11. 11.
    Hoyhtya M, Fridman R, Komarek D, Porter-Jordan K, Stetler-Stevenson WG, Liotta LA, Liang CM (1994) Immunohistochemical localization of matrix metalloproteinase-2 and its specific inhibitor TIMP-2 in neoplastic tissues with monoclonal antibodies. Int J Cancer 56:500–505Google Scholar
  12. 12.
    Monteagudo C, Merino M, San-Juan J, Liotta LA, Stetler-Stevenson WG (1990) Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. Am J Pathol 136:585–592Google Scholar
  13. 13.
    Nakajima M, Welch DR, Belloni PN, Nicholson GL (1987) Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res 47:4869–4876Google Scholar
  14. 14.
    Okada A, Bellocq J-P, Rouyer N, Chenard M-P, Rio M-C, Chambon P, Basset P (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 USA 92:2730–2734Google Scholar
  15. 15.
    Polette M, Clavel C, Cockett M, Girod de Bentzmann S, Murphy G, Birembaut P (1993) Detection and localization of mRNAs encoding matrix metalloproteinases and their tissue inhibitor in human breast pathology. Invasion Metastasis 13:31–37Google Scholar
  16. 16.
    Polette M, Gilbert N, Stas I, Nawrocki B, Noel A, Remacle A, Stetler-Stevenson WG, Birembaut P, Foidart JM (1994) Gelatinase A expression and localization in human breast cancers. An in situ hybridization study and immunohistochemical detection using confocal microscopy. Virchows Arch 424:641–645Google Scholar
  17. 17.
    Poulsom R, Hanby AM, Pignatelli M, Jeffrey RE, Longcroft JM, Rogers L (1993) Expression of gelatinase A and TIMP2 mRNAs in desmoplastic fibroblasts in both mammary carcinomas and basal cell carcinomas of the skin. J Clin Pathol 46:429–436Google Scholar
  18. 18.
    Sato H, Takino T, Okada Y, Cao J, Shinigawa A, Yamamoto E, Seiki M (1994) A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature 370:61–65Google Scholar
  19. 19.
    Soini Y, Hurskainen T, Hoyhtya M, Oikarinen A, Autio-Harmanainen H (1994) 72 kD and 92 kD type IV collagenase, type IV collagen and laminin mRNAs in breast cancer: a study by in situ hybridization. J Histochem Cytochem 42:945–951Google Scholar
  20. 20.
    Thompson EW, Yu M, Bueno J, Lin L, Maiti SN, Palao-Marco FL, Pulyaeva H, Tamborlane JW, Tirgari R, Wapnir, Azzam H (1994) Collagen-induced MMP-2 activation in human breast cancer. Breast Cancer Res Treat 31:357–370Google Scholar
  21. 21.
    Tryggvason K, Hoyhtya M, Pyke C (1993) Type IV collagenase in invasive tumors. Breast Cancer Res Treat 24:209–218Google Scholar
  22. 22.
    Urbanski SJ, Edwards DR, Maitland A, Leco KJ, Watson A, Kossakowska AE (1992) Expression of metalloproteinases and their inhibitors in primary pulmonary carcinomas. Br J Cancer 66:1188–1194Google Scholar
  23. 23.
    Ward RV, Atkinson SJ, Slocombe PM, Docherty AJP, Reynolds JJ, Murphy G (1991) Tissue inhibitor of metalloproteinases-2 inhibits the activation of 72 kDa progelatinase by fibroblast membranes. Biochim Biophys Acta 1079:242–246Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • M. Polette
    • 1
  • B. Nawrocki
    • 1
  • J. -M. Tournier
    • 1
  • P. Birembaut
    • 1
  • C. Gilles
    • 2
  • H. Sato
    • 3
  • M. Seiki
    • 3
  1. 1.I.N.S.E.R.M. U.314, C.H.R., Maison BlancheReimsFrance
  2. 2.Department of Cell Biology, Vincent T. Lombardi Cancer Research CenterGeorgetown University Medical CenterWashingtonUSA
  3. 3.Department of Molecular Virology and Oncology, Cancer Research Institute, School of MedicineKanazawa UniversityIshikawaJapan

Personalised recommendations