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Article

Cancer cells release anaphylatoxin C5a from C5 by serine protease to enhance invasiveness

  • Authors:
    • Hidetoshi Nitta
    • Yoji  Murakami
    • Yoshihiro  Wada
    • Masatoshi  Eto
    • Hideo  Baba
    • Takahisa  Imamura
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterological Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan, Department of Urology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan, Department of Molecular Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
  • Pages: 1715-1719
    |
    Published online on: July 18, 2014
       https://doi.org/10.3892/or.2014.3341
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Abstract

Anaphylatoxin C5a indirectly fosters cancer cells through recruitment of myeloid-derived suppressor cells (MDS) for inhibiting antitumor CD8+ T cells and induction of neovascularization. We recently found activation of cancer cells by C5a directly via the C5a-receptor (C5aR; CD88) to enhance invasiveness. Thus, C5a possibly contributes to cancer progression rather than elimination. C5a generation in cancer tissues has been reported; however, the mechanism is not fully elucidated. Cancer cell expression of complement regulatory molecules suggests inefficient C5a generation through activation of the complement system in response to cancer cells. To explore another C5a generation mechanism in cancer tissues, we examined cancer cells for C5a-releasing activity from C5. C5a was present in C5-supplemented culture media of cancer cells including C5aR-expressing cells, and the media enhanced C5aR-expressing cancer cell invasion, which was abolished by anti-C5a antibody. The C5a-releasing activity was absent in the supernatants of the media and was inhibited by aprotinin, a serine protease inhibitor, and decanoyl-Arg-Val-Lys-Arg-chloromethylketone but not by inhibitors specific for cysteine, acid, or metal proteases. These results indicated C5a release from C5 by a cancer cell membrane-bound serine protease that can cleave peptide bonds at the carboxy-terminal site of paired basic amino acid residues. Cancer cell C5a release from the complement-immobilized plasma supported feasibility of this cancer cell protease-dependent C5a generation in cancer tissues. The new mechanism of C5a generation suggests self-activation of C5aR-expressing cancer cells to enhance invasiveness and induction of MDS recruitment and neovascularization to create a microenvironment favorable for cancer progression.
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Copy and paste a formatted citation
Spandidos Publications style
Nitta H, Murakami Y, Wada Y, Eto M, Baba H and Imamura T: Cancer cells release anaphylatoxin C5a from C5 by serine protease to enhance invasiveness. Oncol Rep 32: 1715-1719, 2014.
APA
Nitta, H., Murakami, Y., Wada, Y., Eto, M., Baba, H., & Imamura, T. (2014). Cancer cells release anaphylatoxin C5a from C5 by serine protease to enhance invasiveness. Oncology Reports, 32, 1715-1719. https://doi.org/10.3892/or.2014.3341
MLA
Nitta, H., Murakami, Y., Wada, Y., Eto, M., Baba, H., Imamura, T."Cancer cells release anaphylatoxin C5a from C5 by serine protease to enhance invasiveness". Oncology Reports 32.4 (2014): 1715-1719.
Chicago
Nitta, H., Murakami, Y., Wada, Y., Eto, M., Baba, H., Imamura, T."Cancer cells release anaphylatoxin C5a from C5 by serine protease to enhance invasiveness". Oncology Reports 32, no. 4 (2014): 1715-1719. https://doi.org/10.3892/or.2014.3341
Copy and paste a formatted citation
x
Spandidos Publications style
Nitta H, Murakami Y, Wada Y, Eto M, Baba H and Imamura T: Cancer cells release anaphylatoxin C5a from C5 by serine protease to enhance invasiveness. Oncol Rep 32: 1715-1719, 2014.
APA
Nitta, H., Murakami, Y., Wada, Y., Eto, M., Baba, H., & Imamura, T. (2014). Cancer cells release anaphylatoxin C5a from C5 by serine protease to enhance invasiveness. Oncology Reports, 32, 1715-1719. https://doi.org/10.3892/or.2014.3341
MLA
Nitta, H., Murakami, Y., Wada, Y., Eto, M., Baba, H., Imamura, T."Cancer cells release anaphylatoxin C5a from C5 by serine protease to enhance invasiveness". Oncology Reports 32.4 (2014): 1715-1719.
Chicago
Nitta, H., Murakami, Y., Wada, Y., Eto, M., Baba, H., Imamura, T."Cancer cells release anaphylatoxin C5a from C5 by serine protease to enhance invasiveness". Oncology Reports 32, no. 4 (2014): 1715-1719. https://doi.org/10.3892/or.2014.3341
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