Skip to main content
Log in

Expression and localization of 92 kDa type IV collagenase/gelatinase B (MMP-9) in human gliomas

  • Research Papers
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Matrix metalloproteinases play an important regulatory role in tissue morphogenesis, cell differentiation and motility, and tumor cell invasiveness. We have recently demonstrated elevated activity of the 92 kDa type IV collagenase (MMP-9) in human glioblastoma and in the present study examine the relative amounts of MMP-9 protein and mRNA in human gliomas and as well as the distribution of MMP-9 in human glioma tumors in vivo. Using an enzyme-linked immunosorbent assay for the quantitative determination of MMP-9 protein, we found that levels were significantly higher in malignant astrocytomas, especially in glioblastoma multiforme, than in normal brain tissues and low-grade gliomas. In addition, the amount of MMP-9 mRNA, as determined by northern blot analysis was higher in anaplastic astrocytomas and glioblastoma multiforme than in normal brain tissue and low-grade gliomas. Immunocytochemical staining for MMP-9 showed strong cytoplasmic immunoreactivity in the tumor cells and the proliferating endothelial cells of glioblastoma multiforme and anaplastic astrocytomas. The staining intensity was lower in low-grade astrocytomas, and was undetectable or very low in normal brain astrocytes. The results indicate that expression of MMP-9 is dramatically upregulated in highly malignant gliomas and correlates with the highly malignant progression of human gliomas in vivo, and support a role for the MMP-9 in facilitating the invasiveness seen in malignant gliomas in vivo.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bjerkvig R, Laerum OD and Mella O, 1986, Glioma cell interactions with fetal rat brain aggregates in vitro and with brain tissue in vivo. Cancer Res, 46, 4071–9.

    PubMed  CAS  Google Scholar 

  2. Russel DC and Rubinstain LJ, 1989, Pathology of Tumors of the Nervous System, 5th ed. London: Edward Arnold.

    Google Scholar 

  3. Gleave JR, 1986, Surgery for primary brain tumors. In: Blehen NM, ed. Tumors of the Brain. Berlin: Springer-Verlag, pp. 101–120.

    Google Scholar 

  4. Liotta LA, 1984, Tumor invasion and metastases: role of the basement membrane. Am J Pathol, 117, 339–48.

    PubMed  CAS  Google Scholar 

  5. Kwaan HC, 1992, The plasminogen-plasmin system in malignancy. Cancer Metastasis Rev, 11, 291–311.

    Article  PubMed  CAS  Google Scholar 

  6. Goldfarb RH and Liotta LA, 1986, Proteolytic enzymes in cancer invasion and metastasis. Semin Thromb Hemostasis, 12, 294–307.

    CAS  Google Scholar 

  7. Liotta LA, Steeg PS and Stetler-Stevenson WG, 1991, Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell, 64, 327–36.

    Article  PubMed  CAS  Google Scholar 

  8. Woessner JF, 1991, Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J, 5, 2145–54.

    PubMed  CAS  Google Scholar 

  9. Nagase H, Ogata Y, Suzuki K, Enghild JJ and Salvensen G, 1991, Substrate specificities and activation mechanisms of matrix metalloproteinases. Biochem Soc Trans, 19, 715–8.

    PubMed  CAS  Google Scholar 

  10. Sato H and Seiki M, 1993, Regulatory mechanism of 92-kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene, 8, 395–405.

    PubMed  CAS  Google Scholar 

  11. Stetler-Stevenson WG, Krutzsch HC and Liotta LA, 1989, Tissue inhibition of metalloproteinase (TIMP-2). A new member of the metallproteinase inhibitor family. J Biol Chem, 264, 17374–8.

    PubMed  CAS  Google Scholar 

  12. Hibbs MS, Hoidal JR and Kang AH, 1987, Expression of a metalloproteinase that degrades native type V collagen and denatured collagens by cultured human alveolar macrophages. J Clin Invest 80, 1644–50.

    PubMed  CAS  Google Scholar 

  13. Liotta LA and Stetler-Stevenson WG, 1990, Metalloproteinases and cancer invasion. Semin Cancer Biology, 1, 99–106.

    CAS  Google Scholar 

  14. Schultz RM, Silberman S, Persky B, Bahkoski AS and Carmichael DF, 1988, Inhibition by human recombinant tissue inhibitor of metallproteinases of human amnion invasion and lung colonization by murine B16-F10 melanoma cells. Cancer Res, 48, 5539–45.

    PubMed  CAS  Google Scholar 

  15. Wang M and Stearns ME, 1988, Blocking of collagenase secretion by estramustine during in vitro tumor cell invasion. Cancer Res, 48, 6262–71.

    PubMed  CAS  Google Scholar 

  16. Paganetti PA, Caroni P and Schwab ME, 1988, Glioblastoma infiltration into central nervous system tissue in vitro: involvement of a metalloproteinase. J Cell Biol, 107, 2281–91.

    Article  PubMed  CAS  Google Scholar 

  17. Vaithilingam IS, McDonald W, Stroude EC, Cook RA and Del Maestro RF, 1992, Proteolytic activity during the growth of C6 astrocytoma in the murine spheroid implantation model. Can J Neurol Sci, 19, 17–22.

    PubMed  CAS  Google Scholar 

  18. Apodaca G, Rutka JT, Bouhana K, et al. 1990, Expression of metalloproteinases and metalloproteinase inhibitors by fetal astrocytes and glioma cells. Cancer Res, 50, 2322–9.

    PubMed  CAS  Google Scholar 

  19. Rao JS, Steck PA, Mohanam S, Stetler-Stevenson WG, Liotta LA and Sawaya R, 1993, Elevated levels of M, 92,000 type IV collagenase in human brain tumors. Cancer Res, 53, 2208–11.

    PubMed  CAS  Google Scholar 

  20. Rao JS, Steck PA, Tofilon P, et al. 1994, Role of plasminogen activator and of 92-kDa type 1 IV collagenase in glioblastoma invasion using an in vitro matrigel model. J Neuro-Oncol, 18, 129–38.

    Article  CAS  Google Scholar 

  21. Kleihus P, Burger PC and Schneithauer BW, 1993, The new WHO classification of brain tumours. Brain Pathol, 3, 255–68.

    Google Scholar 

  22. Nakajima M, Welch DR, Belloni PN and Nicolson GL, 1987, Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell and clones of differing metastatic potentials. Cancer Res, 47, 4869–76.

    PubMed  CAS  Google Scholar 

  23. Juarez J, Clayman G, Nakajima M, et al. 1993, Role and regulation of expression of 92-kDa type-IV collagenase (MMP-9) in two invasive squamous-cellcarcinoma cell lines of the oral cavity. Int J Cancer, 55, 10–18.

    PubMed  CAS  Google Scholar 

  24. Chomczynski P and Sacchi N, 1987, Single-step method of RNA isolation by acid quanidinium thiocyanatephenol-chloroform extraction. Anal Biochem, 162, 156–9.

    Article  PubMed  CAS  Google Scholar 

  25. Matrisian LM, 1992, The matrix-degrading metalloproteinases. Bioessays, 14, 455–63.

    Article  PubMed  CAS  Google Scholar 

  26. Salo T, Turpeenniemi-Hujanen T and Tryggvason K, 1985, Tumor-promoting phorbol esters and cell proliferation stimulate secretion of basement membrane (type IV) collagen-degrading metalloprotease by human fibroblasts. J Biol Chem, 260, 8526–31.

    PubMed  CAS  Google Scholar 

  27. Salo T, Liotta LA, Keski J, Turpeenniemi-Hujanen T and Tryggvason K, 1982, Secretion of basement membrane collagen degradation enzyme and plasminogen activator by transformed cells-role in metastasis. Int J Cancer, 30, 669–73.

    PubMed  CAS  Google Scholar 

  28. Bernhard EJ, Gruber SB and Muschel RJ, 1994, Direct evidence linking expression of matrix metalloproteinase (92-kDa gelatinase/collagenase) to the metastatic phenotype in transformed rat embryo cells. Proc Natl Acad Sci USA, 91, 4293–7.

    Article  PubMed  CAS  Google Scholar 

  29. Muller D, Breathnach R, Eagelmann A, et al. 1991, Expression of collagenase-related metalloproteinase genes in human lung or head and neck tumours. Int J Cancer, 48, 550–56.

    PubMed  CAS  Google Scholar 

  30. Monteagudo C, Merino MJ, San-Juan J, Liotta LA and Stetler-Stevenson WG, 1990, Immunohistochemical distribution of type IV collagenase in normal, benign and malignant breast tissue. Am J Pathol, 136, 585–92.

    PubMed  CAS  Google Scholar 

  31. Hewitt RE, Leach IH, Powe DG, et al. 1991, Distribution of collagenase and tissue inhibitor of metalloproteases (TIMP) in colorectal tumors. Int J Cancer, 49, 666–72.

    PubMed  CAS  Google Scholar 

  32. Nakagawa T, Kubota T, Kubota M, et al. 1994, Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors. J Neurosurg, 81, 69–77.

    PubMed  CAS  Google Scholar 

  33. Okada Y, Tsuchiya H, Shimizu H, et al. 1990, Induction and stimulation of 92-kDa gelatinase/type IV collagenase production in osteosarcoma and fibrosarcoma cell lines by tumor necrosis factor α. Biochem Biophys Res Commun, 171, 610–17.

    Article  PubMed  CAS  Google Scholar 

  34. Shima I, Sasaguri Y, Kusukawa J, et al. 1993, Production of matrix metalloproteinase 9 (92-kDa gelatinase) by human oesophageal squamous cell carcinoma in response to epidermal growth factor. Br J Cancer, 67, 721–7.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rao, J.S., Yamamoto, M., Mohaman, S. et al. Expression and localization of 92 kDa type IV collagenase/gelatinase B (MMP-9) in human gliomas. Clin Exp Metast 14, 12–18 (1996). https://doi.org/10.1007/BF00157681

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00157681

Keywords

Navigation