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A novel laminin‐induced lysophosphatidic acid autocrine loop in the migration of ovarian cancer cells
Author(s) -
Sengupta Saubhik,
Xiao Yi-Jin,
Xu Yan
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-1145fje
Subject(s) - autocrine signalling , lysophosphatidic acid , cell migration , cancer research , microbiology and biotechnology , laminin , cancer cell , autotaxin , ovarian cancer , biology , chemistry , receptor , extracellular matrix , cell , cancer , biochemistry , genetics
We have reported previously that levels of lysophosphatidic acid (LPA) are elevated in the blood and ascites from patients with ovarian cancer. LPA stimulates proliferation of ovarian cancer cells and has been proposed as an autocrine growth factor. Here, we show that a novel autocrine loop of LPA promotes the migration of ovarian cancer cells, which is a critical step of tumor metastasis. We report that laminin, but not other extracellular matrix proteins, induces LPA production in ovarian cancer cells. A neutralizing antibody against β 1 integrin and a calcium‐independent phospholipase A 2 ‐specific inhibitor, HELSS, block both LPA production and the haptotactic activity of laminin. Exogenously added LPA restores the migratory ability of HEY ovarian cancer cells to laminin. These data suggest that laminin‐induced cell migration is mediated by LPA. We further show that a specific receptor for LPA, LPA 3 , is required for mediating the chemotactic activity of LPA. In addition, we show that cytosolic PLA 2 is required for cell migration and its activation is phosphatidylinositol‐3 kinase‐dependent. These findings have revealed a new mechanism of crosstalk between a β 1 integrin receptor and a G protein‐coupled receptor.