| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2039883 | Cell Reports | 2014 | 11 Pages |
•Complement proteins are secreted by cancer cells•Complement knockdown in cancer cells reduces cell proliferation and cancer growth•Activation of the complement system in tumor directly enhances tumor growth
SummaryWe 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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