title: Lysophosphatidic acid stimulates fas ligand microvesicle release from ovarian cancer cells.
abstract: 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.
authors.affiliation: Department of Immunology, University of Illinois at Chicago, Chicago 60612, USA.
authors.forename: Yuru
authors.initials: Y
authors.lastname: Meng
authors.forename: Shijun
authors.initials: S
authors.lastname: Kang
authors.forename: David A
authors.initials: DA
authors.lastname: Fishman
mesh_terms: D015153:Blotting, Western; D003599:Cytoskeleton / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008870:Microtubules / Q000502:physiology; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008246:Lysophospholipids; D008562:Membrane Glycoproteins; C032881:lysophosphatidic acid