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Epithelial Ovarian Cancer Cells Secrete Functional Fas Ligand¹

Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven Connecticut 06520

The Fas/Fas ligand (FasL) system has been suggested to play an important role in the establishment of an immune privilege status of the tumor by inducing Fas-mediated apoptosis in tumor-specific lymphocytes. However, the role of cell surface-expressed FasL in tumor cell protection has recently become controversial. In this study, we have demonstrated that ascites-derived epithelial ovarian cancer cells lack membranal FasL but constitutively secrete whole, intracellular FasL (37 kDa) via the release of microvesicles. In contrast, normal ovarian surface epithelial cells express, but do not secrete, FasL. We have also identified a heavily glycosylated form of secreted FasL (48 kDa), associated with microvesicles isolated directly from the ascites fluid of patients with ovarian cancer. Following the disruption of the microvesicle membrane, both the 37-kDa and 48-kDa forms of secreted FasL were able to trigger Fas-mediated apoptosis in Jurkat T cells. These results suggest that the release of secreted FasL, and not the membrane form, may provide a mechanism by which tumors might counterattack Fas-bearing immune cells, thus facilitating their escape from immune surveillance and promoting tumor cell survival.

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