Autocrine Effects of Tumor-Derived Complement

Min Soon Cho; Hernan G. Vasquez; Rajesha Rupaimoole; Sunila Pradeep; Sherry Wu; Behrouz Zand; Hee-Dong Han; Cristian Rodriguez-Aguayo; Justin Bottsford-Miller; Jie Huang; Takahito Miyake; Hyun-Jin Choi; Heather J. Dalton; Cristina Ivan; Keith Baggerly; Gabriel Lopez-Berestein; Anil K. Sood; Vahid Afshar-Kharghan

doi:10.1016/j.celrep.2014.02.014

Cell Reports (Mar 2014)

Autocrine Effects of Tumor-Derived Complement

Min Soon Cho,
Hernan G. Vasquez,
Rajesha Rupaimoole,
Sunila Pradeep,
Sherry Wu,
Behrouz Zand,
Hee-Dong Han,
Cristian Rodriguez-Aguayo,
Justin Bottsford-Miller,
Jie Huang,
Takahito Miyake,
Hyun-Jin Choi,
Heather J. Dalton,
Cristina Ivan,
Keith Baggerly,
Gabriel Lopez-Berestein,
Anil K. Sood,
Vahid Afshar-Kharghan

Affiliations

Min Soon Cho: Department of Benign Hematology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Hernan G. Vasquez: Department of Benign Hematology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Rajesha Rupaimoole: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Sunila Pradeep: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Sherry Wu: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Behrouz Zand: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Hee-Dong Han: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Cristian Rodriguez-Aguayo: Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Justin Bottsford-Miller: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Jie Huang: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Takahito Miyake: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Hyun-Jin Choi: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Heather J. Dalton: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Cristina Ivan: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Keith Baggerly: Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Gabriel Lopez-Berestein: Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Anil K. Sood: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
Vahid Afshar-Kharghan: Department of Benign Hematology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA

DOI: https://doi.org/10.1016/j.celrep.2014.02.014
Journal volume & issue: Vol. 6, no. 6
pp. 1085 – 1095

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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