Skip to main content
Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 1997 Jul;123(7):402–406. doi: 10.1007/BF01240124

Concentrations of lysosomal cysteine proteases are decreased in renal cell carcinoma compared with normal kidney

Heidrun Kirschke 1,, Tobias Clausen 1, Barbara Göhring 2, Dagmar Günther 1, Edwin Heucke 1, Friedemann Laube 1, Eckhard Löwe 1, Heinz Neef 3, Henriette Papesch 1, Skadi Peinze 1, Gunnar Plehn 1, Udo Rebmann 2, Ari Rinne 4, Roland Rüdrich 1, Ekkehard Weber 1
PMCID: PMC12201149  PMID: 9260593

Abstract

Renal cell carcinoma contains significantly lower concentrations of the lysosomal cysteine proteases, cathepsins B, C, H, L and S, than does normal kidney, as shown by several methods, such as activity determination, enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry. The same low levels of enzyme activity and concentration have been determined in renal cell carcinoma metastases in the lung. Our results on the decreased concentration of cysteine peptidases at the protein level would seem to conflict with earlier results on an increased concentration of the cathepsin L mRNA in renal cell carcinoma.

key words: Lysosomal cysteine proteases, Cathepsins, Renal cell carcinoma, Kidney

Abbreviations

ELISA

enzyme-linked immunosorbent assay

FCS

fetal calf serum

NHMec

7-(4-methyl)coumarylamide

NHNap

2-naphthylamide

Z

benzyloxycarbonyl

References

  1. Abrahamson M, Barrett AJ, Salvesen G, Grubb A (1986) Isolation of six cysteine proteinase inhibitiors from human urine. J Biol Chem 261:11282–11289 [PubMed] [Google Scholar]
  2. Baricos WH, Cortez SL, Le QC, Wu LT, Shaw E, Hanada K, Shah SV (1991) Evidence suggesting a role for cathepsin L in an experimental model of glomerulonephritis. Arch Biochem Biophys 288:468–472 [DOI] [PubMed] [Google Scholar]
  3. Barrett AJ, Kirschke H (1981) Cathepsin B, cathepsin H, and cathepsin L. Methods Enzymol 80:535–561 [DOI] [PubMed] [Google Scholar]
  4. Brömme D, Rinne R, Kirschke H (1991) Tight-binding inhibition of cathepsin S by cystatins. Biomed Biochim Acta 50:631–635 [PubMed] [Google Scholar]
  5. Chauhan SS, Goldstein LJ, Gottesman MM (1991) Expression of cathepsin L in human tumors. Cancer Res 51:1478–1481 [PubMed] [Google Scholar]
  6. Chauhan SS, Popescu NC, Ray D, Fleischmann R, Gottesman MM, Troen BR (1993) Cloning, genomic organization, and chromosomal localization of human cathepsin L. J Biol Chem 268:1039–1045 [PubMed] [Google Scholar]
  7. Gottesman MM (1978) Transformation-dependent secretion of a low molecular weight protein by murine fibroblasts. Proc Natl Acad Sci USA 75:2767–2771 [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Heidtmann HH, Salge U, Havemann K, Kirschke H, Wiederanders B (1993) Secretion of a latent, acid activatable cathepsin L precursor by human non-small cell lung cancer cell lines. Oncol Res 5:441–451 [PubMed] [Google Scholar]
  9. Homma K, Kurata S, Natori S (1994) Purification, characterization, and cDNA cloning of procathepsin L from the culture medium of NIH-Sape-4, an embryonic cell line ofSarcophaga peregrina (flesh fly), and its involvement in the differentiation of imaginal discs. J Biol Chem 269:15258–15264 [PubMed] [Google Scholar]
  10. Kasai M, Shirasawa T, Kitamura M, Ishidoh K, Kominami E, Hirokawa K (1993) Proenzyme form of cathepsin L produced by thymic epithelial cells promotes proliferation of immature thymocyte in the presence of II-1, II-7 and anti-CD3 antibodies. Cell Immunol 150:124–136 [DOI] [PubMed] [Google Scholar]
  11. Kirschke H, Peinze S, Laube F, Weber E (1995) Processing and secretion of cathepsin S by normal and transformed cells. In: Suzuki M, Hiwasa T (eds) Proteases involved in cancer. Monduzzi Editore, Bologna, pp 75–79 [Google Scholar]
  12. Langner J, Ansorge S, Bohley P, Kirschke H, Hanson H (1971) Intracellular protein breakdown. I. Activity determinations of endopeptidases using protein substrates. Acta Biol Med Ger 26:935–951 [PubMed] [Google Scholar]
  13. Olbricht CJ, Fink M, Gutjahr E (1991) Alterations in lysosomal enzymes of the proximal tubule in gentamicin nephrotoxicity. Kidney Int 39:639–646 [DOI] [PubMed] [Google Scholar]
  14. Rescheleit DK, Rommerskirch WJ, Wiederanders B (1996) Sequence analysis and distribution of two new human cathepsin L splice variants. FEBS Lett 394:345–348 [DOI] [PubMed] [Google Scholar]
  15. Rozhin J, Robinson D, Stevens MA, Lah TT, Honn KV, Ryan RE, Sloane BF (1987) Properties of a plasma membrane-associated cathepsin B-like cysteine proteinase in metastatic melanoma variants. Cancer Res 47:6620–6628 [PubMed] [Google Scholar]
  16. Scaddan PB, Dufresne MJ (1993) Characterization of cysteine proteases and their endogenous inhibitors in MCF-7 and adriamycinresistant MCF-7 human breast cancer cells. Invasion Metastasis 13:301–313 [PubMed] [Google Scholar]
  17. Schaefer L, Gilge U, Heidland A, Schaefer RM (1994) Urinary excretion of cathepsin B and cystatins as parameters of tubular damage. Kidney Int 46 [Suppl 47]:S64-S67 [PubMed] [Google Scholar]
  18. Sheahan K, Shuja S, Murnane MJ (1989) Cysteine protease activities and tumor development in human colorectal carcinoma. Cancer Res 49:3809–3814 [PubMed] [Google Scholar]
  19. Weber E, Günther D, Laube F, Wiederanders B, 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 [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Werle B, Ebert W, Klein W, Spiess E (1994) Cathepsin B in tumors, normal tissue and isolated cells from the human lung. Anticancer Res 14:1169–1176 [PubMed] [Google Scholar]

Articles from Journal of Cancer Research and Clinical Oncology are provided here courtesy of Springer

RESOURCES