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Lysophosphatidic acid stimulates fas ligand microvesicle release from ovarian cancer cells

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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.

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Abbreviations

FasL:

Fas ligand

LPA:

Lysophosphatidic acid

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Authors and Affiliations

  1. Department of Immunology, University of Illinois at Chicago, Chicago, 60612, USA

    Yuru Meng & Shijun Kang

  2. Department of Obstetrics and Gynecology, New York University School of Medicine, 550 First Avenue, NBV9N28, New York, NY, 10016, USA

    David A. Fishman

Authors
  1. Yuru Meng
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  2. Shijun Kang
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  3. David A. Fishman
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Corresponding author

Correspondence to David A. Fishman.

Additional information

This work was supported by NCI UO1CA85133, NCI P50 CA83639, NIH R01 CA89503, NIH-RO1CA82562, and NIH RO1 CA01015.

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Meng, Y., Kang, S. & Fishman, D.A. Lysophosphatidic acid stimulates fas ligand microvesicle release from ovarian cancer cells. Cancer Immunol Immunother 54, 807–814 (2005). https://doi.org/10.1007/s00262-004-0642-5

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  • DOI: https://doi.org/10.1007/s00262-004-0642-5

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