Epithelial ovarian cancer cells secrete functional Fas ligand.
Epithelial ovarian cancer cells secrete functional Fas ligand.
复制标题
DOI：
--
复制
发表时间：
2003-09
期刊：
影响因子：
11.2
通讯作者：
V. Abrahams;Shawn Straszewski;M. Kamsteeg;B. Hanczaruk;P. Schwartz;T. Rutherford;G. Mor
中科院分区：
文献类型：
--
作者：
V. Abrahams;Shawn Straszewski;M. Kamsteeg;B. Hanczaruk;P. Schwartz;T. Rutherford;G. Mor
Fas/Fas配体（FasL）系统通过诱导肿瘤特异性淋巴细胞凋亡，在肿瘤免疫赦免状态的建立中发挥重要作用。然而，细胞表面表达的FasL在肿瘤细胞保护中的作用最近变得有争议。在这项研究中，我们已经证明，腹水来源的上皮性卵巢癌细胞缺乏膜FasL，但组成性分泌整个，细胞内的FasL（37 kDa）通过微泡的释放。相反，正常卵巢表面上皮细胞表达但不分泌FasL。我们还鉴定了一种高度糖基化的分泌型FasL（48 kDa），与直接从卵巢癌患者腹水中分离的微泡相关。在微囊泡膜破裂后，37-kDa和48-kDa形式的分泌型FasL都能够触发Jurkat T细胞中Fas介导的凋亡。这些结果表明，分泌型FasL的释放，而不是膜形式，可能提供了一种机制，肿瘤可能会反击Fas携带免疫细胞，从而促进他们逃避免疫监视和促进肿瘤细胞的生存。
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.