 | LYSOPHOSPHOLIPIDS AND EICOSANOIDS IN BIOLOGY AND PATHOPHYSIOLOGY
Copyright © 2000 by the New York Academy of Sciences
description
Annals of the New York Academy of Sciences 905:188-208 (2000)
© 2000 New York Academy of Sciences
Lysophospholipid Growth Factors in the Initiation, Progression, Metastases, and Management of Ovarian Cancer
XIANJUN FANGa,b,
DOUGLAS GAUDETTEb,
TATSURO FURUIb,
MULING MAOb,
VERONICA ESTRELLAb,
ASTRID EDERb,
TERRI PUSTILNIKb,
TAKAYO SASAGAWAb,
RUTHIE LAPUSHINb,
SHIANGXING YUb,
ROBERT B. JAFFEc,
JON R. WIENERb,
JAMES R. ERICKSONd,e AND
GORDON B. MILLSb
bDepartment of Molecular Oncology, Division of Medicine, Department of Gynecologic Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA
cCenter for Reproductive Sciences, University of California at San Francisco, San Francisco, California 94143, USA
dAtairgin Technologies Incorporated, Irvine, California 92618, USA
aAddress for correspondence: Xianjun Fang, Ph.D., Department of Molecular Oncology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Box 317, Houston, TX 77030. Voice: 713/745-1195; fax: 713/794-1807.
xianjunfang{at}mdanderson.org
eFormerly of LXR Biotechnology Incorporated, Richmond, CA 94804.
Levels of lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC) are elevated in the plasma and ascites of ovarian cancer patients, but not in most other tumor types. LPA increases cell proliferation, cell survival, resistance to cisplatin, cell shrinkage, and production of vascular endothelial growth factor, urokinase plasminogen activator, and LPA itself in ovarian cancer cells, but not in normal ovarian surface epithelial cells. PSP24 and members of the endothelial differentiation gene (EDG) family (EDG1, EDG2, EDG4, and EDG7) of G protein-coupled receptors mediate LPA signaling. Ovarian cancer cell lines do not express EDG1 mRNA, have variable EDG2 mRNA and protein levels, and frequently exhibit elevated levels of EDG4 mRNA and protein, suggesting that EDG4 may contribute to the deleterious effects of LPA in ovarian cancer. In contrast, activation of the EDG2 LPA receptor on ovarian cancer cells may lead to apoptosis and counter the effects of other LPA receptors. Thus, the development of agonists and antagonists for the appropriate spectrum of LPA receptors may alter proliferation, apoptosis, or response to therapy of ovarian cancer cells. Indeed, over 60% of all current drugs target the G protein-coupled family of receptors, making the LPA receptor family a "drugable" target. LPC, although not as thoroughly studied, increases cellular proliferation and mediates multiple other functions through unique signaling pathways.
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