Abstract 1496: Changes in white adipose tissue progenitor populations with ovarian cancer

Abstract

Abstract Ovarian cancer is the fourth leading cause of cancer death in women and has the highest mortality rate of all gynecological malignancies. Among the greatest risk factors are age, reproductive history, hormone therapy, and more recently suggested, obesity. Currently, the mechanism for how obesity contributes to ovarian cancer is unknown, but there is potential for adipose tissue-associated cells to be key players in this pathogenesis. The stromal vascular fraction (SVF) of white adipose tissue is a rich source of various stem and progenitor cell populations, which can be recruited by cancer cells to enhance cancer progression and metastatic potential. Studies have shown that there is an increase in progenitor populations within the adipose tissue with obesity and age, two risk factors for ovarian cancer. While it has been shown that SVF cells can contribute to cancer, it has not been determined what impact cancer progression has on adipose tissue. It is plausible that ovarian cancer has systemic effects, which may influence cell populations within adipose tissue to promote metastases. Our lab has developed a spontaneously transformed murine ovarian surface epithelial (MOSE) cell model that becomes increasingly more aggressive with repeated passaging. Late passage cells rapidly form tumors when injected into mice, while earlier passage cells do not. Using this model, we investigated the effects of ovarian cancer on systemic changes in progenitor populations. Firefly luciferase-expressing MOSE-L TICv cells, a highly aggressive, metastatic tumor-initiating cell variant were injected into the peritoneal cavity of C57BL/6 mice and stem/progenitor populations and various immune cell populations within the perigonadal white adipose tissue, blood, ascites, and omentum were immunophenotyped by flow cytometry. Changes in gene expression profiles were also analyzed using quantitative real-time PCR. Interestingly, peritoneal dissemination changed the profile and composition of progenitor populations in the various tissues, suggesting that ovarian cancer does have a more widespread impact, affecting the blood and perigonadal adipose tissue. Additionally, co-culture studies demonstrate that MOSE cells and SVF associated cells positively interact enhancing tumor spheroid growth and provide survival signals. This suggests a synergistic relationship between the MOSE and SVF cells. These discoveries may provide a mechanistic link for the detrimental impact of obesity on ovarian cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1496. doi:1538-7445.AM2012-1496