Lysophosphatidic Acid Regulation and Roles in Human Prostate Cancer.

摘要

Lysophosphatidic acid (LPA) is a major mitogen in serum that regulates an array of cellular processes related to pathogenesis of cancer, especially ovarian, prostate and breast carcinomas. LPA stimulates proliferation by increasing cell cycle progression and suppression of apoptosis, as well as enhancing tumor cell invasion and angiogenesis (1, 2). Several reports have shown that LPA can transactivate the EGF tyrosine kinase receptor (3-5) by stimulating metalloproteinase processing of proHB-EGF to EGF (4). This novel cross communication between different signaling systems is not only important for the growth promoting activity of LPA (3, 5), but also may provide a clue to its pathophysiological role in prostate cancer (4). Progress in understanding LPA actions has accelerated with the discovery that it is a ligand of several U protein coupled cell surface receptors (GPCRs), previously identified as members of the endothelial differentiation gene (EDG) family, and hereafter referred to as LPA receptors. To date, three LPARs have been identified, EDG-2/LPA1, EDG-4/ LPA2, and EDG-7/LPA3 (6; 7). These are differentially expressed, coupled to a variety of U-proteins, and thus regulate diverse cellular responses. Expression of LPA receptors correlates with more advanced prostate cancer cell lines (8). Thus, LPA may play a critical role in the pathophysiology of prostate cancer.