Lysosomal Cysteine Peptidases and Malignant Tumours

  • Heidrun Kirschke
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 421)


Putative biological functions of lysosomal cysteine peptidases especially of cathepsins B and L in tumour progression have recently been considered in several reviews and the respective literature has been compiled1–5. Here, only some aspects of the extracellular and intracellular functions of these enzymes and the correlation of expression of cathepsins L and H with the malignancy of tumours should be discussed.


Metastatic Tumour Murine Cell Line Intracellular Function Thyroid Epithelial Cell Lysosomal Cysteine Peptidase 
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  1. 1.
    L Kane, S.E., and Gottesman, M.M., 1990, The role of cathepsin L in malig nant transformation, Semin. Cancer Biol. I: 127–136.Google Scholar
  2. 2.
    Sloane, B.F., Moin, K., Krepela, E., and Rozhin, J., 1990, Cathepsin B and its endogenous inhibitors: the role in tumor malignancy, Cancer Metast. Rev. 9: 333–352.CrossRefGoogle Scholar
  3. 3.
    Gottesman, M.M., 1993, Cathepsin L and cancer, in: Proteolysis and Protein Turnover, Bond, J.S., and Barrett, A.J., eds., Portland Press, London and Chapel Hill, 247–251.Google Scholar
  4. 4.
    Berquin, I.M., and Sloane, B.F., 1996, Cathepsin B expression in human tumors, in: Intracellular Protein Catabolism, Suzuki, K., and Bond, J.S., eds., Plenum Press, New York and London, 281–294.CrossRefGoogle Scholar
  5. 5.
    Kirschke, H., Barrett, A.J., and Rawlings, N.D., 1995, Proteinases 1: Lyso somal cysteine proteinases, Protein Profile 2: 1587–1643.Google Scholar
  6. 6.
    Schmitt, M., Goretzki, L., Jänicke, F., Calvete, J., Eulitz, M., Kobayashi, H., Chucholowski, N., and Graeff, H., 1991, Biological and clinical relevance of the urokinase-type plasminogen activator (uPA) in breast cancer, Biomed. Biochim. Acta 50: 731–741.PubMedGoogle Scholar
  7. 7.
    McCoy, K., Gal, S., Schwartz, R.H., and Gottesman, M.M., 1988, An acid protease secreted by transformed cells interferes with antigen processing, J. Cell Blot. 106: 1879–1884.CrossRefGoogle Scholar
  8. 8.
    Kasai, M., Shirasawa, T., Kitamura, M., Ishido, K., Kominami, E., and Hi-rokawa, K., 1993, Proenzyme form of cathepsin L produced by thymic epi thelial cells promotes proliferation of immature thymocytes in the presence of IL-1, IL-7, and anti-CD3 antibody, Cell. Immunol. 150: 124–136.PubMedCrossRefGoogle Scholar
  9. 9.
    Weber, E., Günther, D., Laube, F., Wiederanders, B., and Kirschke, H.. 1994, Hybridoma cells producing antibodies to cathepsin L have greatly reduced potential for tumour growth, J. Cancer Res. Clin. Oncol. 120: 564–567.PubMedCrossRefGoogle Scholar
  10. 10.
    Homma, K., Kurata, S.. and Natori, S., 1994, Purification, characterization, and cDNA cloning of procathepsin L from the culture medium of NIH-Sape- 4, an embryonic cell line of Sarcophaga peregrino (flesh fly), and its invol vement in the differentiation of imaginal discs,. 1. Biol. Chem. 269: 15258–15264.Google Scholar
  11. 11.
    Dehrmann, F.M., Coetzer, T.H.T., Pike, R.N., and Dennison, C., 1995, Ma turc cathepsin L is substantially active in the ionic milieu of the extracellular medium, Arch. Biochem. Biophy.s. 324: 93–98.CrossRefGoogle Scholar
  12. 12.
    Turk. B., Dolenc, I., Turk, V., and Bieth, J.G., 1993, Kinetics of the pH-indu ced inactivation of human cathepsin L, Biochemistry 32: 375–380.CrossRefGoogle Scholar
  13. 13.
    Brix, K.. Lemansky, P., and Herzog, V., 1996, Evidence for extracellularly acting cathepsins mediating thyroid hormone liberation in thyroid epithelial cells, Endocrinology 137: 1963–1974.PubMedCrossRefGoogle Scholar
  14. 14.
    Rozhin, J.. Sameni, M., Ziegler, G., and Sloane, B.F.. 1994, Pericellular pH affects distribution and secretion of cathepsin B in malignant cells, Cancer Res. 54 6517–6525.Google Scholar
  15. 15.
    Ebert, W., Werle, B., Ebert, E., Kos, J., Lah, T., and Abrahamson, M., 1996, Cathepsins and cystatins. prognostic factors in human lung cancer, 11th International Conference on Proteolysis and Protein Turnover: Turku (Poster Abstract N°132).Google Scholar
  16. 16.
    Scaddan, P.B., and Dufresne, M.J., 1993, Characterization of cysteine pro teases and their endogenous inhibitors in MCF-7 and adriamycin-resistant MCF-7 human breast cancer cells, Invar. Metast. 13: 301 313.Google Scholar
  17. 17.
    Sheahan, K., Shuja. S.. and Murnane, M.J., 1989, Cysteine protease ac tivities and tumor development in human colorectal carcinoma. Cancer Res. 49: 3809–3814.Google Scholar
  18. 18.
    Adenis, A., Huet. G., Zerimech. F., Hecquet, B., Balduyck, M., and Peyrat, J.P., 1995, Cathepsin B. L, and D activities in colorectal carcinomas: rela tionship with clinico-pathological parameters, Cancer Lett. 96: 267–275.PubMedCrossRefGoogle Scholar
  19. 19.
    Rozhin,.1., Wade. R.L., Bonn. K.V., and Sloane, B.F., 1989, Membrane-as-sociated cathepsin L: a role in metastasis of melanomas, Biochem. Biophys. Res. Commun. 164: 556–561.CrossRefGoogle Scholar
  20. 20.
    Qian, F., Bajkowski, A.S., Steiner, D.F., Chan, S.J., and Frankfater, A., 1989, Expression of five cathepsins in murine melanomas of varying metas tatic potential and normal tissues, Cancer Res. 49: 4870–4875.PubMedGoogle Scholar
  21. 21.
    Kageshita, T., Yoshi i, A., Kimura, T., Maruo, K., Ono, T., Himeno, M.. and Nishimura, Y., 1995, Biochemical and immunohistochemical analysis of cathepsins B, H, L and D in human melanocytic tumours,. Arch. Dermatol. Res. 287: 266–272.PubMedCrossRefGoogle Scholar
  22. 22.
    Sivaparvathi, M., Yamamoto, M., Nicolson, G.L., Gokaslan, Z.L., Fuller, G.N., Liotta, L.A., Sawaya, R., and Rao, J.S., 1996, Expression and immu nohistochemical localization of cathepsin L during the progression of human gliomas. Clin. Exp. Metast. 14: 27–34.CrossRefGoogle Scholar
  23. 23.
    Denhardt, D.T., Greenberg, A.H.. Egan, S.E., Hamilton, R.T., and Wright, J.A., 1987, Cysteine proteinase cathepsin L expression correlates closely with the metastatic potential of H-ras-transformed murine fibroblasts, On cogene 2: 55–59.Google Scholar
  24. 24.
    Chambers, A.F., Colella, R., Denhardt, D.T., and Wilson, S.M., 1992, In-creased expression of cathepsins L and B and decreased activity of their in hibitors in metastatic, ras-transformed NIH 3T3 cells, Mol. Carcinog. 5: 238–245.PubMedCrossRefGoogle Scholar
  25. 25.
    Sivaparvathi, M., Sawaya, R., Gokaslan, Z.L., Chintala, K.S., and Rao, J.S., 1996, Expression and the role of cathepsin H in human glioma progression and invasion, Cancer Lett. 104: 121–126.PubMedCrossRefGoogle Scholar
  26. 26.
    Gabrijeléié, D., Svetic, B., Spaié, D., Skrk, J., Budihna, M., Dolenc, I., Po povié, T., Cotié, V., and Turk, V., 1992, Cathepsins B, H and L in human breast carcinoma, Eue J. Clin. Chem. Clin. Biochem. 30: 69–74.Google Scholar
  27. 27.
    Murnane, M.J., Cai, J., Shuja, S., Coté, L., Del Re, E., lacobuzio-Donahue, C., Kim, K., and Sheahan, K., 1995, Changing patterns of proteolytic ex pression with colorectal tumor progression, in: Proteases Involved in Cancer, Suzuki, M., and Hiwasa, T., eds., Monduzzi Editore, Bologna, 11–26.Google Scholar
  28. 28.
    Yagel, S., Warner, A.H., Nellans, H.N., Lala, P.K., Waghorne, C., and Den hardt, D.T., 1989, Suppression by cathepsin L inhibitors of the invasion of amnion membranes by murine cancer cells, Cancer Res. 49: 3553–3557.PubMedGoogle Scholar
  29. 1.
    Bond, J. S., and A. J. Barrett, 1993, Proteolysis and protein turnover, Proceeding of the 9th I(.’OP Meeting. Williamsburg, Virginia, U. S. A., Portland Press Proceedings. page X IV.Google Scholar
  30. 2.
    Hoesch, Kurt, 1921, Emil Fischer. sein Leben und sein Werk, Verlag Chemie, G.m.b.11.. Berlin und Leipzig, 480 pages.Google Scholar
  31. 3.
    Abderhalden. Emil. 1906. Lehrbuch der Physiologischen Chemie, Urbahn und Schwarzenberg, Berlin. Wien, 787 pages.Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Heidrun Kirschke
    • 1
  1. 1.Institute of Physiological Chemistry Faculty of MedicineMartin-Luther University of Halle-WittenbergHalle (Saale)Germany

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