Abstract 177: Obesity promotes growth of ovarian cancer through adipose stem cells

Abstract

Abstract Introduction: Intraperitoneal spread to visceral adipose is a frequent event and a major cause of morbidity and mortality in women with ovarian cancer. Excess visceral adiposity increases the risk of ovarian cancer. We hypothesized that obesity effects may be mediated by the adipose-derived stem cell population (ASC) to enhance the initiation and progression of ovarian cancer. Results: Intraperitoneally injected ID8 ovarian cancer cells grew significantly faster in mice with diet-induced obesity (p<0.05). To determine if ASC mediated this effect, ASC were then isolated from the subcutaneous (SC-ASC) and visceral adipose (V-ASC) of mice with diet-induced obesity and lean mice. ASC from all sources expressed same mesenchymal cell surface markers and similarly increased ID8 cell proliferation and survival following paclitaxel treatment. There was no significant difference in ID8 migration in response to ASC conditioned media from lean and obese mice. ASC from obese mice exhibited impaired differentiation into adipocytes and osteocytes in-vitro as compared to ASC from lean mice. 106 renilla luciferase expressing ID8 were co-injected intra-peritoneally with equal number of different ASC isolates into C57Bl6 mice. SC-ASC from obese mice promoted growth of intraperitoneal tumor and the formation of metastasis as compared to SC-ASC from lean mice (p<0.05). There was no significant difference in the effect of V-ASCs from obese and lean mice on ID8 cells. There was trend towards more rapid tumor growth in mice injected with V-ASC as compared to SC-ASC from lean mice. Ascites volume was highest in mice injected with SC-ASC derived from obese mice. SC-ASC from obese mice increased tumor vascularity while ASC from obese mice increased the formation of intra-tumoral perilipin expressing adipocytes. Conclusions: SC-ASC from obese mice promoted tumor growth more than ASC from lean mice suggesting that obesity alters the ASC population to enhance tumor-promoting effects. Obese derived ASC exhibit impaired differentiation potential, which may be linked to tumor promoting effects. Future studies will focus on understanding the mechanisms by which obesity alters the ASC population to impact tumor progression. Citation Format: Yan Zhang, Travis Solley, Karen Lu, Caimiao Wei, Alesandra Nowicka, Ann Klopp. Obesity promotes growth of ovarian cancer through adipose stem cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 177. doi:10.1158/1538-7445.AM2014-177