Abstract 5323: Fractalkine receptor CX3CR1 regulates peritoneal dissemination of ovarian carcinoma

Abstract

Abstract Epithelial ovarian carcinoma (EOC) is the deadliest gynecologic malignancy largely due to the metastatic disease. EOC metastases spread by shedding the malignant cells off of the ovarian surface and seeding tissues and organs of the peritoneal cavity. Currently used therapies, a combination of chemotherapy and surgery, fail to keep most patients in the remission. Mechanistic understanding of the biology of EOC metastasis will facilitate development of new therapeutic approaches. Our previous data demonstrated that fractalkine receptor (CX3CR1) is expressed by EOC cells and can support cell migration and proliferation. Moreover, our previous data suggested that CX3CR1-positive EOC cells can adhere to the CX3CL1-postive peritoneal mesothelial cells in in vitro assay. Thus, we hypothesized that CX3CL1/CX3CR1 axis could be important for peritoneal dissemination of metastatic EOC. To test this hypothesis, we performed short-term ex vivo and in vivo adhesion assay, as well as long-term metastasis formation assay. Expression of CX3CR1 in EOC cells was downregulated in SKOV-3 using shRNA. Both CX3CR1 shRNA-expressing and scrambled shRNA-expressing EOC cells were seeded atop of mouse peritoneum and omentum tissues in the ex vivo assay and allowed to adhere for up to 24 h. CX3CR1 shRNA-expressing and scrambled shRNA-expressing EOC cells were intraperitoneally injected into abdomens of athymic nude mice for 4 h following sacrifice of the animals and examination of the peritoneal organs and tissues for green fluorescence. Data analysis has demonstrated that downregulation of CX3CR1 in EOC cells led to a significant decrease of adhesion in these assays. Furthermore, parental SKOV-3 as well as CX3CR1 shRNA-, scrambled shRNA-, and vector shRNA-expressing cells were intraperitoneally injected into athymic nude mice and allowed to form metastasis for 10 weeks. As a result, we observed very small omental metastatic lesions in three out of six animals injected with CX3CR1 shRNA-expressing cells. In opposite, all of the control groups developed gross intraperitoneal metastasis in many organs and tissues. Our data suggest that CX3CR1 may be one of the key factors that determine peritoneal dissemination of EOC. 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 5323. doi:1538-7445.AM2012-5323