Abstract 650: An isogenic experimental model identifies β-catenin as a molecular target in ovarian cancer metastasis

Abstract

Abstract Ovarian cancer metastasis is closely associated with unfavorable outcomes, yet the underlying mechanisms remain obscure. Here we establish an isogenic model that could mimic the spontaneous metastasis of human ovarian cancer. Given that tumor cells are heterogeneous in nature, an isogenic pair of highly metastatic (HM) and non-metastatic (NM) cell lines with opposite metastatic capabilities was derived using in vitro and in vivo selection. Incorporation of the luciferase gene into the cell pair allowed non-invasive monitoring of the metastatic events by bioluminescent imaging in vivo. Orthotopic implantation of HM into the ovarian bursa of NOD/SCID mice resulted in metastases within the peritoneum with ascites formation, thus representing the major dissemination pattern of human ovarian cancer cells. However, NM failed to form detectable metastases, although it was tumorigenic at the ovarian bursa. In comparison with NM, HM displayed higher spheroid-forming ability and had higher expression of stemness marker genes, which are characteristics of cancer stem-like population. By proteomic profiling and pathway analysis, HM is found to be enriched in the oncogenic β-catenin signaling, a pathway elevated in ovarian cancer metastases. Tumor initiation and metastasis of HM was dramatically impaired when β-catenin was specifically knocked down. We further demonstrated that β-catenin could down-regulate the expression of Dicer, a major component of the microRNA machinery. These results together suggest that this model could help to delineate the molecular mechanisms for ovarian cancer metastasis, and provide clinically relevant insights to target metastasizing ovarian cancer cells. Citation Format: Sally KY To, Alice ST Wong. An isogenic experimental model identifies β-catenin as a molecular target in ovarian cancer metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 650.