Autocrine Effects of Tumor-Derived Complement

Min Soon Cho(The University of Texas MD Anderson Cancer Center), Hernan G. Vasquez(The University of Texas MD Anderson Cancer Center), Rajesha Rupaimoole(The University of Texas MD Anderson Cancer Center), Sunila Pradeep(The University of Texas MD Anderson Cancer Center), Sherry Y. Wu(The University of Texas MD Anderson Cancer Center), Behrouz Zand(The University of Texas MD Anderson Cancer Center), Hee‐Dong Han(The University of Texas MD Anderson Cancer Center), Cristian Rodriguez‐Aguayo(The University of Texas MD Anderson Cancer Center), Justin Bottsford-Miller(The University of Texas MD Anderson Cancer Center), Jie Huang(The University of Texas MD Anderson Cancer Center), Takahito Miyake(The University of Texas MD Anderson Cancer Center), Hyun Jin Choi(The University of Texas MD Anderson Cancer Center), Heather J. Dalton(The University of Texas MD Anderson Cancer Center), Cristina Ivan(The University of Texas MD Anderson Cancer Center), Keith Baggerly(The University of Texas MD Anderson Cancer Center), Gabriel Lopez‐Berestein(The University of Texas MD Anderson Cancer Center), Anil K. Sood(The University of Texas MD Anderson Cancer Center), Vahid Afshar‐Kharghan(The University of Texas MD Anderson Cancer Center)
Cell Reports
March 1, 2014
10.1016/j.celrep.2014.02.014
Cited by 221Open Access
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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.

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