Abstract B72: CX3CR1, a fractalkine receptor, can regulate peritoneal dissemination of epithelial ovarian cancer cells

Abstract Epithelial ovarian carcinoma (EOC) is a leading cause of death from gynecologic malignancies mainly due to metastasis. EOC metastases spread by shedding the malignant cells off from the ovarian surface and seeding to organs and tissues in the peritoneal cavity. The current standard of care, a combination of chemotherapy and surgery, fails to keep patients in remission. Thus, mechanistic understanding of the biology of EOC metastasis and identification of novel targetable molecules are crucial for the development of improved therapeutic approaches. Fractalkine receptor (CX3CR1) belongs to a chemokine family of G-protein coupled receptors. CX3CR1 is expressed by EOC cells and promotes cell migration and proliferation. CX3CR1-positive EOC cells have been shown to adhere to the CX3CL1-positive peritoneal mesothelial cells in vitro. Thus, we hypothesized that CX3CL1/CX3CR1 axis could be important for peritoneal dissemination of metastatic EOC. In order to test this hypothesis, we performed short-term ex vivo and in vivo adhesion assays, as well as long-term metastasis formation assay. We found that EOC cells prefer omentum to other peritoneal tissues during the short-term in vivo and ex vivo adhesion. Importantly, reduction of CX3CR1 expression in EOC cells resulted in significantly reduced peritoneal adhesion. Furthermore, reduced adhesion correlated with the ability of EOC cells to form overt metastasis. Microenvironmental milieu has been histologically evaluated for stromal cells in the omentum expressing CX3CL1. Taken together, our data indicate that fractalkine signaling is one of the central regulators of EOC metastasis. Citation Format: Jia Xie, Hilal Gurler, Joanna Burdette, Maria Barbolina. CX3CR1, a fractalkine receptor, can regulate peritoneal dissemination of epithelial ovarian cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B72.