Abstract 4887: Omentin: A novel adipokine in the omental microenvironment associated with ovarian cancer progression

Abstract

Abstract Advanced stage serous ovarian cancer metastasizes preferentially to the omentum, which is a well-vascularized fold of peritoneal tissue and is a major site of intra-abdominal fat accumulation, suggesting that the omental microenvironment is a favorable niche for ovarian cancer cells. The 5-year survival drops to below 50% for the cancer cases that spread beyond the pelvis to the omentum. It has also become apparent that obesity contributes to a poor clinical outcome. The mechanisms by which omental adipose tissue promotes tumor growth and disease progression are not entirely clear. Using transcriptome profiling analysis on the microdissected adipose tissue from patients with benign gynecologic diseases and from patients with advanced high-grade serous ovarian cancer (HGSOC), we identified a gene signature for ovarian cancer associated omental adipose tissue, suggesting that alteration of these genes in the ovarian cancer associated omental adipose tissue may generate a permissive microenvironment to support ovarian cancer growth. Among genes that are significantly up- or down-regulated in ovarian cancer associated adipose tissue compared with the normal adipose tissue, we seek to focus on evaluating the role of omentin (Intestinal Lactoferrin Receptor ITLN1) in ovarian cancer progression since it is a novel adipokine that is predominantly expressed and secreted by visceral adipose tissue and is barely detectable in subcutaneous fats. Our data showed for the first time that omentin was expressed predominantly by the mesothelial cells covering the visceral adipose tissue but not by other cell types in the omental adipose tissue. Interestingly, we showed that circulating omentin level is significantly lower in patients with HGSOC compared with those in the BMI matched healthy individuals. In addition, using monolayer culture models, we demonstrated that omentin suppressed ovarian cancer motility and invasion potential directly and ovarian cancer growth only in the presence of adipocytes. We also showed that omentin can increase insulin-dependent glucose up-take in adipocytes and omentin expression can be down-regulated by co-culturing with ovarian cancer cells and in the presence of TNF-α. The study provides the first evidence that ovarian cancer cells modify the visceral adipose tissue through down-regulation of omentin to facilitate their growth in the omental microenvironment. Citation Format: Chi Lam Au Yeung, Ngai Na Co, Michaela Onstad, Tsz-Lun Yeung, Cecilia S. Leung, Rosemarie Schmandt, Karen H. Lu, Samuel C. Mok. Omentin: A novel adipokine in the omental microenvironment associated with ovarian cancer progression. [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 4887. doi:10.1158/1538-7445.AM2014-4887