Abstract A32: Fractalkine receptor, CX3CR1, Can regulate the response of ovarian carcinoma cells to radiation therapy

Abstract

Abstract Ovarian carcinoma is a leading cause of death from gynecologic malignancies. The current treatment, a combination of chemotherapy and radiation, fails to keep patients in remission. Therefore, mechanistical understanding of the disease and modifications of the therapy could offer benefits to overcome current problems and combat the disease. Fractalkine receptor (CX3CR1) belongs to a chemokine family of G protein-coupled receptors, the most frequently and successfully drug-targeted group of proteins. Previous publications show that interaction of chemokines with their receptors plays an important role in homing distant metastasis, as well as promoting migration, adhesion, and proliferation in many types of cancer. X-Ray radiotherapy is a well-developed method of anti-cancer treatment, however, it is seldom used against ovarian carcinoma due to multiple reasons, including dose-related effects. Hence, strategies for reducing the dose of radiation while keeping its efficiency at a therapeutically effective level could provide rational for developing approaches for a more wide-spread use of this method. Our data indicate that transient downregulation of CX3CR1 in p53-null cells and p53-mutant cells but not in p53 wild-type ovarian carcinoma cell lines can lead to approximately 50% sensitization to x-ray radiation, as determined by the clonogenic assay. Importantly, our in vivo studies demonstrated that a transient downregulation of CX3CR1 in combination with x-ray radiation led to approximately 50% reduction of tumor weights compared to either downregulation of CX3CR1 or x-ray radiation alone. We are currently characterizing the detailed mechanisms behind the CX3CR1-dependent radiosensitization, including those related to changes in cell cycle progression, involvement of cellular reactive oxygen species accumulation and regulation of DNA single and double strand break repair. Taken together, our date indicate that disruption of the CX3CR1 signaling could sensitize ovarian carcinoma to radiation therapy. Citation Format: Jia Xie, Hilal Gurler, Maria Barbolina. Fractalkine receptor, CX3CR1, Can regulate the response of ovarian carcinoma cells to radiation therapy. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A32.