Abstract 3191: Immune cell bound MUC16 (CA125): A novel diagnostic marker for ovarian cancer

Abstract

Abstract MUC16 is a cell surface mucin expressed at high levels by epithelial ovarian cancer cells. Following proteolytic cleavage, cell surface MUC16 (csMUC16) is shed (sMUC16) in the extracellular milieu and is detected in the serum of cancer patients as the tumor marker CA125. csMUC16 acts as an adhesion molecule and facilitates peritoneal metastasis of ovarian tumors. Both sMUC16 and csMUC16 also protect cancer cells from cytotoxic responses of natural killer (NK) cells. In a previous study, we demonstrated that sMUC16 binds to a specific subset of NK cells. Here, we demonstrate that in addition to NK cells, sMUC16 also binds to B cells and monocytes isolated from the peripheral circulation and the peritoneal fluid. I-type lectin, Siglec-9, is identified as the sMUC16 receptor on these immune cells. The inhibitory receptor Siglec-9 is expressed on approximately 30-40% of CD16pos/CD56dim NK cells, 20-30% of B cells and >95% of monocytes. sMUC16 binds to the majority of the Siglec-9pos NK cells, B cells and monocytes. sMUC16 is released from the immune cells following neuraminidase treatment. While sMUC16 binds to Siglec-9, it has no affinity for another I-type lectin, Siglec-7. Experiments with Siglec-9 transfected Jurkat cells and monocytes isolated from healthy donors demonstrate that immune cells can bind to ovarian tumor cells via Siglec-9-csMUC16 interaction. sMUC16-Siglec-9 binding is a high affinity and event and the mucin is detected on the surface of the patient-derived immune cells even after the cells have been cultured in vitro in media that does not contain any sMUC16. The MUC16 mucin is also expressed by the human decidua and higher circulating levels of this molecule (measured as CA125) are detected in peripheral circulation of pregnant women. Flow cytometry analysis of immune cells from pregnant women indicates that MUC16 can be detected on the surface of specific subsets of immune cells even when the serum CA125 levels are very low or undetectable. Furthermore, we have observed that sMUC16 is detected on distinct subsets of NK cells of women with preeclampsia as compared to healthy pregnant women and patients with ovarian tumors. Our on-going studies are focused on monitoring sMUC16 binding to specific subsets of immune cells to determine if this information can be used to devise a novel assay for the diagnosis and monitoring of ovarian tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3191. doi:10.1158/1538-7445.AM2011-3191