Abstract 3953: The omental microenvironment promotes ovarian cancer metastasis and enhances CD-133 mediated self-assembly of ovarian cancer spheroids.

Abstract Objective: Recent evidence suggests that the human omentum functions as a niche that promotes ovarian cancer metastasis. We investigated the role of the omentum in sequestration and enhancement of ovarian cancer stem cells. Materials and Methods: To further explore this unique phenomenon, we examined the ability of cells isolated from ovarian cancer implants at distinct anatomic sites to create multicellular aggregates known as spheroids. In ovarian and other cancers, spheroids promote a pluripotent phenotype and play a critical role in metastasis. Results: We found that ovarian cancer cells recovered from omentum express higher levels of the pluripotency-associated antigen CD133 and create larger numbers of more rapidly growing spheroids than cells recovered from the tubo-ovarian complex. Although CD133+ or CD44+ ovarian cancer cells are equally capable of creating large spheroids, spheroids self-assembled from CD133+ ovarian cancer cells are significantly more tumorigenic in vivo than CD44+, CD133−CD44− or unsorted cells. We also found that spheroids self-assembled from CD133+ ovarian cancer cells migrate to both the ovary and omentum of SCID mice and that CD133+ ovarian cancer cells induce intraperitoneal xenografts when inoculated subcutaneously. In contrast, our data indicate that spheroids self-assembled from CD44+ cells preferentially induce tumor adjacent to their inoculation site. Targeting CD133 expression inhibits the in vivo tumorigencity of spheroids assembled from A2780 ovarian cancer cells. Conclusions: In addition to delineating novel pathways by which the omental microenvironment promotes ovarian cancer metastasis, these findings establish a new paradigm for understanding how ovarian cancer stem cells can be potentially maintained or regenerated within the peritoneal cavity. Strategies to target the omental niche have enormous potential to improve ovarian cancer outcomes. Citation Format: Molly A. Brewer, Guigin Sun, Matthew Anderson, Fanliang Meng, Mei Zhong. The omental microenvironment promotes ovarian cancer metastasis and enhances CD-133 mediated self-assembly of ovarian cancer spheroids. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3953. doi:10.1158/1538-7445.AM2013-3953