Lysophosphatidic acid stimulates fas ligand microvesicle release from ovarian cancer cells
Lysophosphatidic acid stimulates fas ligand microvesicle release from ovarian cancer cells
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DOI：
10.1007/s00262-004-0642-5
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发表时间：
2005-08-01
影响因子：
5.8
通讯作者：
Fishman, DA
中科院分区：
文献类型：
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作者：
Meng, YR;Kang, SJ;Fishman, DA
以往的研究表明溶血磷脂酸（LPA）可上调卵巢癌细胞表面Fas配体（FasL）的表达。在这项研究中，我们的目的是研究可溶性FasL（sFasL）分泌的小膜微泡后LPA刺激，并分析细胞骨架重组在LPA诱导的FasL转运的作用。用LPA刺激卵巢癌细胞，收获用过的培养基，浓缩并超离心以收集上清液和沉淀。Western blot结果显示，卵巢癌细胞释放的sFasL为成熟型，并以小的膜微泡形式释放。流式细胞术显示，大多数分泌的微囊泡在其膜上含有FasL，并且这些小的膜微囊泡对活化的人T淋巴细胞具有生物活性。微管破坏剂诺考达唑，而不是肌动蛋白丝破坏剂细胞松弛素D预处理阻断了LPA刺激的表达FasL的小膜微泡释放，表明微管在FasL微泡运输和胞吐中起着重要作用。LPA可能通过对抗腹腔抗肿瘤免疫而促进卵巢癌转移。
Previous reports support that lysophosphatidic acid (LPA) upregulates Fas ligand (FasL) cell surface presentation on the ovarian cancer cells. In this study, we aim to investigate soluble FasL (sFasL) secretion associated with the small membrane microvesicles upon LPA stimulation, and to analyze the roles of cytoskeletal reorganization in FasL transport induced by LPA. Ovarian cancer cells were stimulated with LPA and spent media were harvested, concentrated, and ultracentrifugated to collect the supernatant and pellet. Western blot suggested that sFasL released from ovarian cancer cells were the mature form, and these sFasL are released with the small membrane microvesicles. Flow cytometry showed that the majority of microvesicles secreted contained FasL on their membrane, and these small membrane microvesicles are bioactive against activated human T lymphocytes. The microtubule-disrupting reagent nocodazole, not the actin-filament-disrupting reagent cytochalasin D pretreatment blocked FasL-expressing small membrane microvesicle release stimulated by LPA, suggesting that microtubules play an essential role in FasL microvesicle transport and exocytosis. LPA may promote ovarian cancer metastasis by counterattacking peritoneal cavity anti-tumor immunity.