Role of phospholipase D in agonist-stimulated lysophosphatidic acid synthesis by ovarian cancer cells.

Abstract:

:Lysophosphatidic acid (LPA) is a receptor-active lipid mediator with a broad range of biological effects. Ovarian cancer cells synthesize LPA, which promotes their motility, growth, and survival. We show that a murine homolog of a human protein previously reported to hydrolyze LPA is a highly selective detergent-stimulated LPA phosphatase that can be used to detect and quantitate LPA. Use of this protein in novel enzymatic assay demonstrates that SK-OV-3 ovarian cancer cells release physiologically relevant levels of biologically active LPA into the extracellular space. LPA release is markedly increased by nucleotide agonists acting through a P2Y4 purinergic receptor. Promotion of LPA formation by nucleotides is accompanied by stimulation of phospholipase D (PLD) activity. Overexpression of both PLD1 and PLD2 in SK-OV-3 cells produces active enzymes, but only overexpression of PLD2 results in significant amplification of both nucleotide-stimulated PLD activity and LPA production. SK-OV-3 cells express and secrete a phospholipase A2 activity that can generate LPA from the lipid product of PLD, phosphatidic acid. Our results identify a novel role for nucleotides in the regulation of ovarian cancer cells and suggest an indirect but critical function for PLD2 in agonist-stimulated LPA production.

journal_name

J Lipid Res

authors

Luquain C,Singh A,Wang L,Natarajan V,Morris AJ

doi

10.1194/jlr.M300188-JLR200

keywords:

subject

Has Abstract

pub_date

2003-10-01 00:00:00

pages

1963-75

issue

10

eissn

0022-2275

issn

1539-7262

pii

M300188-JLR200

journal_volume

44

pub_type

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