Abstract 4990: Complement promotes growth of ovarian cancer.

Abstract

Abstract Objective: The complement system is a component of innate immunity against invading pathogens, but also mediates the cell-cell communication in organ regeneration, angiogenesis, epithelial-mesenchymal transition (EMT) and cell migration. We studied whether the complement system affect tumor growth in ovarian cancer. Materials & Methods: Complement C3 mRNA level was quantified using qRT-PCR in ovarian cancer cell lines and in tumor specimens from patients with ovarian cancer. Small interfering RNA (siRNA) was used to investigate the consequences of C3 gene silencing in vitro and in vivo. Results: C3 was expressed in ovarian cancer cell lines and tumor tissues from patients. Silencing of the C3 gene decreased ovarian cancer cell proliferation, migration and invasion in vitro. In orthotopic murine models of ovarian cancer, C3 siRNA reduced growth of implanted tumors by 60% as was evident by lower number and smaller size of tumor nodules in C3-siRNA treated mice in comparison to those in scrambled siRNA treated control mice (average tumor weight of 0.19 g in C3 siRNA vs. 0.61 g in scrambled siRNA, n=8 in each group, p=0.017; average nodule number of 4.4 in C3 siRNA vs. 11.4 in scrambled siRNA, n=8 in each group, p=0.05; t-test). Consistent with our in vitro and animal studies, ovarian cancer patients with a higher C3 mRNA level in their tumors had a worse prognosis with overall survival rates compared to those with a lower C3 mRNA level (n=75, p=0.03). Conclusion: Our studies revealed a novel role for complement in cancer biology. Cancer cell-derived C3 promotes tumor growth and progression. Our studies might identify the complement system as a new target for the development of new anti-tumor reagents. Citation Format: Min Soon Cho, Hernan G. Vasquez, Hee Dong Han, Sunila Pradeep, Rajesh Rupaimoole, Behrouz Zand, Michael Kroll, Anil K. Sood, Vahid Afshar-Kharghan. Complement promotes growth of ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4990. doi:10.1158/1538-7445.AM2013-4990