Journal of Cancer Research and Clinical Oncology

, Volume 120, Issue 9, pp 564–567 | Cite as

Hybridoma cells producing antibodies to cathepsin L have greatly reduced potential for tumour growth

  • Ekkehard Weber
  • Dagmar Günther
  • Friedemann Laube
  • Bernd Wiederanders
  • Heidrun Kirschke
Rapid Communication

Abstract

Several tumour-forming cell lines are known to secrete the precursor of a lysosomal cysteine proteinase, procathepsin L. The function in tumour growth and proliferation of this neutral-pH-labile proteinase or its precursor outside lysosomes is as yet unknown. Murine myeloma cells (P3X63Ag8.653) secrete procathepsin L and exhibit a high potential for malignant tumour growth and metastasis. Such cells were fused with spleen cells of mice immunized with cathepsin L. Clones of the resulting hybridoma cells continued to secrete procathepsin L, but also secreted the antibody to cathepsin L. Here we show that the hybridoma cells producing an antibody to cathepsin L have, to a great extent, lost the potential that they otherwise exhibit for inducing solid tumours after implantation into mice.

Key words

mAbs to cathepsin L Cathepsin L Procathepsin L Tumour growth Hybridoma cells 

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References

  1. Belleli A, Mattioni M, Rusconi V, Sezzi ML, Belleli L (1990) Inhibition of tumor growth, invasion and metastasis in papain-immunized mice. Invasion Metastasis 10:142–169Google Scholar
  2. Doria G, Agarossi G, Adorini L (1982) Selective effects of ionizing radiations on immunoregulatory cells. Immunol Rev 65:23–54Google Scholar
  3. Gottesman MM (1978) Transformation-dependent secretion of a low molecular weight protein by murine fibroblasts. Proc Natl Acad Sci USA 75:2767–2771Google Scholar
  4. Joseph LJ, Chang LC, Stamenkovich D, Sukhatme VP (1988) Complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L: an abundant transcript induced by transformation of fibroblasts. J Clin Invest 81:1621–1629Google Scholar
  5. Kane SE, Gottesman MM (1990) The role of cathepsin L in malignant transformation. Semin Cancer Biol 1:127–136Google Scholar
  6. Kennett RH (1978) Cell fusion. Methods Enzymol 58:345–359Google Scholar
  7. Kirschke H, Langner J, Wiederanders B, Ansorge S, Bohley P (1977) Cathepsin L—a new proteinase from rat liver lysosomes. Eur J Biochem 74:293–301Google Scholar
  8. Kobayashi H, Ohi H, Sugimura M, Shinohara H, Fujii T, Terao T (1992) Inhibition of in vitro ovarian cancer cell invasion by modulation of urokinase-type plasminogen activator and cathepsin B. Cancer Res 52:3610–3614Google Scholar
  9. Mason RW, Gal S, Gottesman MM (1987) The identification of the major excreted protein (MEP) from a transformed mouse fibroblast cell line as a catalytically active precursor form of cathepsin L. Biochem J 248:449–454Google Scholar
  10. O'Farrell PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250:4007–4021Google Scholar
  11. Troen BR, Gal S, Gottesman MM (1987) Sequence and expression of the cDNA for MEP (major excreted protein), a transformation-regulated secreted cathepsin. Biochem J 246:731–735Google Scholar
  12. Wiederanders B, Kirschke H (1986) Antibodies to rat liver cathepsins: characterization and use for the identification of enzyme precursors. Biomed Biochim Acta 45:1421–1431Google Scholar
  13. Yagel S, Warner AH, Nellans HN, Lala PK, Waghorne C, Denhardt DT (1989) Suppression by cathepsin L inhibitors of the invasion of amnion membranes by murine cancer cells. Cancer Res 49:3553–3557Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Ekkehard Weber
    • 1
  • Dagmar Günther
    • 1
  • Friedemann Laube
    • 1
  • Bernd Wiederanders
    • 2
  • Heidrun Kirschke
    • 1
  1. 1.Institute of Physiological Chemistry, Medical FacultyMartin-Luther-UniversityHalle (Saale)Germany
  2. 2.Institute of Biochemistry, Medical FacultyFriedrich-Schiller-UniversityJenaGermany

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