title: Autocrine effects of tumor-derived complement.
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.
authors.affiliation: Department of Benign Hematology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Min Soon
authors.initials: MS
authors.lastname: Cho
authors.affiliation: Department of Benign Hematology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hernan G
authors.initials: HG
authors.lastname: Vasquez
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Rajesha
authors.initials: R
authors.lastname: Rupaimoole
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sunila
authors.initials: S
authors.lastname: Pradeep
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Zand
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hee-Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Rodriguez-Aguayo
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Bottsford-Miller
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Takahito
authors.initials: T
authors.lastname: Miyake
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Dalton
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ivan
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Baggerly
authors.affiliation: Department 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.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.affiliation: Department 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.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.affiliation: Department of Benign Hematology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: vakharghan@mdanderson.org.
authors.forename: Vahid
authors.initials: V
authors.lastname: Afshar-Kharghan
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000276:immunology; D045744:Cell Line, Tumor; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D003165:Complement System Proteins