Abstract LB-163: Genetic and pharmaceutical approaches for the study of complement factors as alternative therapy for ovarian cancer

Abstract

Abstract Chronic inflammation is now clearly established as a key player in the process of carcinogenesis. Complement factors can be activated under various chronic inflammatory conditions, suggesting that they could contribute in promoting tumor development. However, the role of complement in ovarian cancer (OC) progression remains poorly investigated. OC is the second most common gynecologic cancer and the fourth leading cause of cancer death in women. Developing alternative therapies is required to decrease OC high mortality rate. To determine the role of complement in cancer establishment and progression, we used genetic and pharmaceutical approaches. We first crossed complement component 3 knockout (C3KO) mice with transgenic mice expressing the Simian Virus 40 TAg under the control of the Müllerian Inhibiting Substance type II Receptor promoter (Tg-MISIIR-TAg). Tg-MISIIR-TAg mice develop bilateral OC resembling human serous OC with ∼100% penetrance. We found that C3KO/MISIIR-TAg mice developed no or very small tumors at 16 weeks of age compared to control wild-type C3/MISIIR-TAg and C3/MISIIR-TAg heterozygote littermates. We also found that tumor-infiltrating leukocytes were functionally altered with changes of secretion profiles for cytokines and angiogenic factors. Second, we orthotopically implanted fluorescent ovarian carcinoma cells (MOV1Kat) in Tg-MISIIR-TAg mice treated with complement C5aR inhibitor peptide or control peptide. MOV1 cell line was isolated from Tg-MISIIR-Tag tumor and transducted with a Far-red fluorescent protein, Katushka, using TurboFP635 Lentivirus mammalian vector to permit in vivo optical imaging (IVIS). Our results showed that the pharmacological inhibition of C5a-binding to C5aR receptor promoted tumor regression. Altogether, our results indicated an important and understudied role of complement for ovarian cancer. We propose that complement inhibitors could be used as therapeutic agents for the treatment of ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-163.