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Cell Rep. 2014 Mar 27;6(6):1085-95. doi: 10.1016/j.celrep.2014.02.014. Epub 2014 Mar 6.

Autocrine effects of tumor-derived complement.

Author information

  • 1Department of Benign Hematology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
  • 2Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
  • 3Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
  • 4Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Center for RNAi and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
  • 5Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Center for RNAi and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: asood@mdanderson.org.
  • 6Department of Benign Hematology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: vakharghan@mdanderson.org.

Abstract

We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic T cells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene in cancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PMID:
24613353
[PubMed - indexed for MEDLINE]
PMCID:
PMC4084868
Free PMC Article
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