Skip to main content
Log in

Expression of cysteine protease inhibitors in human gliomas and meningiomas

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

Increased levels of human cysteine proteases have been implicated in the progression of tumors from the premalignant to the malignant state. The physiological activities of these proteases are regulated by their interactions with specific inhibitors. To our knowledge there have been no previous reports about the cysteine protease inhibitors (CPIs) in human brain tumors. In the study reported here, we determined CPI activity during glioma progression and compared that with normal human brain tissue. We also determined CPI activities in meningioma and glioblastoma cell lines in vitro. This activity was significantly higher in normal brain tissue and low-grade glioma than in anaplastic astrocytoma and glioblastoma. CPI activity was significantly higher in benign and atypical meningioma cell extracts in comparison with those from malignant meningiomas and with those from glioblastoma cell lines. After several passages, one benign meningioma cell line showed reduced levels of CPI and increased levels of cathepsin. Our results suggest that decreases in the activities of CPI may contribute to the malignant properties of brain tumors.

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. Jaaskelainen J, Halta M and Servo A, 1986, Atypical and anaplastic meningiomas: radiology, surgery, radiotherapy, and outcome. Surg Neurol, 25, 233–42.

    Google Scholar 

  2. Wilson CB, 1995, Meningiomas: genetics, malignancy and the role of irradiation in their induction and treatment. Schneider Lecture, presented at the American Association of Neurological Surgeons Meeting, San Francisco, 1992.

  3. Sivaparvathi M, Sawaya R, Wang SWet al. 1995, Overexpression and localization of cathepsin B during the progression of human gliomas. Clin Exp Metastasis, 13, 49–56.

    Google Scholar 

  4. Barrett An, 1987, The cystatins: a new class of peptidase inhibitors. Trends Biochem Sci, 12, 193–6.

    Google Scholar 

  5. Lenarcic B, Krasovec M, Ritonja A, Olafsson I and Turk V, 1991, Inactivation of human cystatin C and kiminogen by human cathepsin D. FEBS Lett, 280, 211–15.

    Google Scholar 

  6. Lenarcic B, Kos J, Dolenc I, Lucovnik P, Krizaj I and Turk V, 1988, Cathepsin D inactivates cysteine protease inhibitors cystatins. Biochem Biophys Res Commun, 154, 765–72.

    Google Scholar 

  7. Okamoto H and Greenbaum LM, 1983, Isolation and structure of T-Kinin. Biocehm Biophys Res Commun, 112, 701–7083.

    Google Scholar 

  8. Abrahamson M, Mason RW, Hansson H, Buttle DJ, Grubb A and Ohlsson K, 1991, Human cystatin C role of the N-terminal segment in the inhibition of human cysteine proteinases and in its activation by leucocyte elastase. Biochem J, 273, 621–6.

    Google Scholar 

  9. Moin K, Emmert LT and Sloane BF, 1992, A membrane associated cysteine protease inhibitor from murine hepatoma. FEBS Lett, 309, 279–82.

    Google Scholar 

  10. Barrett, AJ, Davies ME and Grubb A, 1984, The place of human y-trace (cystatin C) amongst the cysteine protease inhibitors. Biochem Biophys Res Commun, 120, 631–6.

    Google Scholar 

  11. Abrahamson M, Barrett AJ, Salvesen G and Grubb A, 1986, Isolation of six cysteine protease inhibitors from human urine. J Biol Chem, 261, 11282–9.

    Google Scholar 

  12. Salvesen G, Parkes C, Abrahamson M, Grubb A and Barrett AJ, 1986, Human low Mr kininogen contains three copies of a cystatine sequence that are divergent in structure and in inhibitory activity for cysteine proteinases. Biochem J, 234, 429–34.

    Google Scholar 

  13. Jarvinen M, Rinnee A and Hopsu-Havu VK, 1987, Human cystatine in normal and diseased tissues: a review. Acta Histochem, 82, 5–18.

    Google Scholar 

  14. Hara K, Kominami E and Katunuma N, 1988, Effect of proteinase inhibitors on intracellular processing of cathepsin B, H and L in rat macrophages. FEBS Lett, 231, 229–31.

    Google Scholar 

  15. Chambers AF, Colella R, Denhardt DT and Wilson SM, 1992, Increased expression of cathepsins L and B, and decreased activity of their inhibitors, in metastatic, ras-transformed NIH 3T3 cells. Mol Carcinogen, 5, 238–45.

    Google Scholar 

  16. McCormick D, 1993, Secretion of cathepsin B by human gliomas in vitro. Neuropathol Appl Neurobiol, 19, 146–51.

    Google Scholar 

  17. Bradford MM, 1976, A rapid and sensitive method for the quantitations of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem, 72, 248–54.

    Google Scholar 

  18. Rozhin J, Wade RL, Honn KV and Sloane BF, 1989, Membrane-associated cathepsin L: a role in metastasis of melanomas. Biochem Biophys Res Commun, 164, 556–61.

    Google Scholar 

  19. Moin K, Emmert LT and Sloane BF, 1992, A membrane associated cysteine protease inhibitor from murine hepatoma. FEBS Lett, 309, 279–82.

    Google Scholar 

  20. Barrett AJ and Kirschke H, 1981, Cathepsin B, cathepsin H and cathepsin L. Meth Enzymol, 80, 535–61.

    Google Scholar 

  21. Kirschke H and Shaw E, 1981, Rapid inactivation of cathepsin L by Z-Phe-Phe-CHN2 and Z-Phe-AlaCHN2. Biochem Biophys Res Commun, 101, 454–8.

    Google Scholar 

  22. Sloane BF, Moin K, Krepela E and Rozhin J, 1990, Cathepsin B and its endogenous inhibitors: the role in tumor malignancy. Cancer Metastasis Rev, 9, 333–52.

    Google Scholar 

  23. Denhardt DT, Greenberg AH, Egan SE, Hamilton RT and Wright JA, 1987, Cysteine proteinase cathepsin L expression correlates closely with the metastatic potential of H-ras-transformed murine fibroblasts. Oncogene, 2, 55–9.

    Google Scholar 

  24. Chauhan SS, Goldstein LJ and Gottesman MM, 1991, Expression of cathepsin L in human tumors. Cancer Res, 51, 1478–81.

    Google Scholar 

  25. Sivaparvathi M, Yamamoto M, Nicolson GL, et al. 1996, Expression and immunohistochemical localization of cathepsin L during the progression of human gliomas. Clin Exp Metastasis, 14, 27–34.

    Google Scholar 

  26. Baricos WH, Zhou Y, Mason RW and Barrett AJ, 1988, Human kidney cathepsin B and L: characterization and potential role in degradation of glomerular basement membrane. Biochem J, 252, 301–4.

    Google Scholar 

  27. Rozhin J, Gomez AP, Ziegler GH, et al. 1990, Cathepsin B to cysteine proteinase inhibitor balance in metastatic cell subpopulations isolated from murine tumors. Cancer Res, 50, 6278–84.

    Google Scholar 

  28. Hawley-Nelson p, Roop DR, Cheng CK, Krieg TM and Yuspa SH, 1988, Molecular cloning of mouse epidermal cystatin A and detection of regulated expression in differentiation and tumorigenesis. Mol Carcino, 1, 202–11.

    Google Scholar 

  29. Ponton A, Coulombe B and Skup D, 1991, Decreased expression of tissue inhibitor of metalloproteinases in metastatic tumor cells leading to increased levels of collagenase activity. Cancer Res, 51, 2138–43.

    Google Scholar 

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

    Google Scholar 

  31. Mohanam S, Wang SW, Rayford A, et al. 1995, Expression of tissue inhibitors of metalloproteinases negative regulators of human glioblastomas invasion in vivo. Clin Exp Metastasis, 13, 57–62.

    Google Scholar 

  32. Pagano M, Capony F and Rochefort H, 1990, In vitro activation of pro-Cathepsin B by Cathepsin D, both secreted by breast cancer cells. Cr Acad Sci Paris 309, 7–12.

    Google Scholar 

  33. Montcourrier P, Mangeat PH, Salazar G, Morisset M, Sahuquet A and Rochefort H, 1990, Cathepsin D in breast cancer cells can digest extracellular matrix in large acid vesicles. Cancer Res, 50, 6045–54.

    Google Scholar 

  34. Monsky WL and Chen W-T, 1993, Proteases of cell adhesion proteins in cancer. Sem Cancer Biol, 4, 251–8.

    Google Scholar 

  35. Sun Q, 1989, Growth stimulation of 3T3 fibroblasts by cystatin. Exp Cell Res, 80, 150–60.

    Google Scholar 

  36. Hiwasa T, Sawada T and Sakiyama S, 1990, Cysteine protease inhibitors and ras gene products share the same biological activities including transforming activity toward NlH/3T3 mouse fibroblasts and the differentiation-inducing activity toward PC12 rat pheochromocytoma cells. Carcinogenesis, 11, 75–80.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sivaparvathi, M., McCutcheon, I., Sawaya, R. et al. Expression of cysteine protease inhibitors in human gliomas and meningiomas. Clin Exp Metast 14, 344–350 (1996). https://doi.org/10.1007/BF00123393

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00123393

Keywords

Navigation