Autocrine Effects of Tumor-Derived Complement

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. Activat...

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Detalles Bibliográficos
Autores principales: Cho, Min Soon, Vasquez, Hernan G., Rupaimoole, Rajesha, Pradeep, Sunila, Wu, Sherry, Zand, Behrouz, Han, Hee-Dong, Rodriguez-Aguayo, Cristian, Bottsford-Miller, Justin, Huang, Jie, Miyake, Takahito, Choi, Hyun-Jin, Dalton, Heather J., Ivan, Cristina, Baggerly, Keith, Lopez-Berestein, Gabriel, Sood, Anil K., Afshar-Kharghan, Vahid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4084868/
https://www.ncbi.nlm.nih.gov/pubmed/24613353
http://dx.doi.org/10.1016/j.celrep.2014.02.014
Descripción
Sumario: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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