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

69 Citations (Scopus)

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
JournalFASEB Journal
Volume17
Issue number11
StatePublished - 2003
Externally publishedYes

Fingerprint

Laminin
Ovarian Neoplasms
Cells
CD29 Antigens
Cell Movement
Calcium-Independent Phospholipase A2
Lysophosphatidic Acid Receptors
Phosphatidylinositol 3-Kinase
lysophosphatidic acid
Extracellular Matrix Proteins
Crosstalk
G-Protein-Coupled Receptors
Neutralizing Antibodies
Ascites
Tumors
Intercellular Signaling Peptides and Proteins
Blood
Chemical activation
Neoplasm Metastasis
Calcium

Cite this

A novel laminin-induced LPA autocrine loop in the migration of ovarian cancer cells. / Sengupta, Saubhik; Xiao, Yi Jin; Xu, Yan.

In: FASEB Journal, Vol. 17, No. 11, 2003, p. 1570-1572.

Research output: Contribution to journalArticle

Sengupta, Saubhik ; Xiao, Yi Jin ; Xu, Yan. / A novel laminin-induced LPA autocrine loop in the migration of ovarian cancer cells. In: FASEB Journal. 2003 ; Vol. 17, No. 11. pp. 1570-1572.
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