Abstract 401: Early immune modulatory events during ovarian cancer outgrowth in the omental fat band (2012)

Abstract Ovarian cancer is the fourth most deadly cancer in women. Typically originating in the layer of epithelial cells surrounding the ovary, cancer cells exfoliate, disseminating throughout the peritoneal cavity. The omental fat band (OFB) has been described as a secondary lymphoid organ, composed of heavily vascularized fatty tissue interspersed with immune cell aggregates. The OFB is also the site of preferential tumor cell adhesion and invasion within the peritoneal cavity, and is removed at the time of surgical debulking in ovarian cancer patients as a preventative measure. Animal studies have shown that ovarian cancer cells home to the omentum as early as 20 minutes post-injection, however the early signaling events that contribute to immune evasion and neoplastic outgrowth have not been fully elucidated. Our lab has developed a spontaneously transformed murine ovarian surface epithelial (MOSE) cell model that, following long-term passaging mimics the progressive stages of ovarian cancer from non-tumorigenic MOSE-E (early) cells to MOSE-L (late) cells which readily disseminate and establish tumors throughout the peritoneum after injection. We have developed two cell variants of the MOSE-L cell line, which differ in their in vivo aggressiveness. The heterogeneous EGFP-expressing MOSE-L IVP2 cell line results in a slowly developing disease state with administration of 1 x 106 cells. In contrast, the MOSE-L firefly luciferase-expressing (FFL) TICv is a highly aggressive tumor-initiating cell variant that results in rapidly disseminating disease with as few as 100 implantable cells. Here we have utilized these cell lines to evaluate early and late changes within the OFB immune microenvironment in order to shed light on both beneficial anti-tumorigenic immune signals, as opposed to signals involved in immune evasion, tumor cell seeding/outgrowth and establishment of aggressive disease states. Specifically, MOSE-E, EGFP∼MOSE-L IVP2 and MOSE-L FFL TICv cells were injected intraperitoneally (IP) into C57BL/6 mice and at 24 h or 4 wks post-injection subsets of mice were euthanized and blood, peritoneal washings, OFB, spleens, perigonadal fat depots were collected for further analysis. Here we describe changes to the OFB and peritoneal serous exudate as a function of tumor cell dissemination using flow cytometry for immunophenotyping and quantitative real-time PCR for gene expression profiling. Preliminary results confirm that ovarian tumor initiating cells preferentially invade the omentum early during cancer metastasis, and are capable of escaping innate immune surveillance mechanisms. In contrast, MOSE-E cells readily home to the OFB early, but are cleared within 7 days. The completion of this study should provide new insights into the initial immunomodulatory events associated with early ovarian cancer seeding and outgrowth within the OFB, a tissue crucial in early ovarian cancer metastasis. 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 401. doi:1538-7445.AM2012-401