In vitro inhibition of matriptase prevents invasive growth of cell lines of prostate and colon carcinoma

  • Authors:
    • Diana Förbs
    • Stefan Thiel
    • Maria C. Stella
    • Anne Stürzebecher
    • Andrea Schweinitz
    • Torsten Steinmetzer
    • Jörg Stürzebecher
    • Kerstin Uhland
  • View Affiliations

  • Published online on: Saturday, October 1, 2005
  • Pages:1061-1070 DOI: 10.3892/ijo.27.4.1061
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Abstract

Matriptase, also known as membrane-type-serine-protease 1 (MT-SP 1), is a type II transmembrane serine protease involved in the activation of the precursor form of hepatocyte growth factor/scatter factor (pro-HGF/SF). Since HGF/SF is a well-known extracellular signal, which plays a key role in the control of invasive growth, we investigated the effects of matriptase inhibition in cell lines derived from colon (DLD-1) or prostate (PC-3) carcinomas. Biochemical analysis showed that matriptase was very efficient in the proteolytic conversion of the inactive HGF/SF precursor into HGF/SF. Inhibition of endogenous matriptase synthesis in DLD-1 or PC-3 cells by specific small interfering RNAs impaired the conversion of pro-HGF/SF into HGF/SF at the cell surface and inhibited cell scattering upon pro-HGF/SF stimulation. The same effect was observed after treatment of these cells with matriptase inhibitors of the 3-amidinophenylalanine-type, CJ-697 or CJ-730. Inhibition of matriptase significantly reduced invasion of the extracellular matrix as well. Interestingly, this reduction was observed even in the presence of pre-activated HGF/SF. It is concluded that matriptase plays a dual-role in the events unleashing the invasive phenotype, one ‘upstream’ from the HGF/SF signalling cascade and one ‘downstream’, most likely at the level of the plasminogen activation system. These data provide a proof of concept for the targeting of matriptase in the search for anti-invasive drugs.

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October 2005
Volume 27 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2015 Impact Factor: 3.018
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APA
Förbs, D., Thiel, S., Stella, M.C., Stürzebecher, A., Schweinitz, A., Steinmetzer, T. ... Uhland, K. (2005). In vitro inhibition of matriptase prevents invasive growth of cell lines of prostate and colon carcinoma. International Journal of Oncology, 27, 1061-1070. http://dx.doi.org/10.3892/ijo.27.4.1061
MLA
Förbs, D., Thiel, S., Stella, M. C., Stürzebecher, A., Schweinitz, A., Steinmetzer, T., Stürzebecher, J., Uhland, K."In vitro inhibition of matriptase prevents invasive growth of cell lines of prostate and colon carcinoma". International Journal of Oncology 27.4 (2005): 1061-1070.
Chicago
Förbs, D., Thiel, S., Stella, M. C., Stürzebecher, A., Schweinitz, A., Steinmetzer, T., Stürzebecher, J., Uhland, K."In vitro inhibition of matriptase prevents invasive growth of cell lines of prostate and colon carcinoma". International Journal of Oncology 27, no. 4 (2005): 1061-1070. http://dx.doi.org/10.3892/ijo.27.4.1061