A novel laminin-induced LPA autocrine loop in the migration of ovarian cancer cells.

Saubhik Sengupta, Yi Jin Xiao, Yan Xu

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

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 beta1 integrin and a calcium-independent phospholipase A2-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, LPA3, is required for mediating the chemotactic activity of LPA. In addition, we show that cytosolic PLA2 is required for cell migration and its activation is phosphatidylinositol-3 kinase-dependent. These findings have revealed a new mechanism of crosstalk between a beta1 integrin receptor and a G protein-coupled receptor.

Original languageEnglish (US)
Pages (from-to)1570-1572
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume17
Issue number11
StatePublished - Aug 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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