Lysophospholipids activate ovarian and breast cancer cells

作者：Yan Juan Xu, X J Fang, Graham Casey, Gordon Brent Mills · 发表于：Biochemical Journal · 年份：1995 · DOI：10.1042/bj3090933 · 被引用次数：285 · 研究领域：Sphingolipid Metabolism and Signaling、Erythrocyte Function and Pathophysiology、Protein Kinase Regulation and GTPase Signaling

We have investigated the effects of phospholipids on activation and proliferation of ovarian and breast cancer cells. Lysophosphatidic acid (LPA), lysophosphatidylserine (LPS) and sphingosylphosphorylcholine (SPC) all induce transient increases in cytosolic free Ca2+ ([Ca2+]i) in both ovarian and breast cancer cell lines. The ability of LPA, LPS and SPC to induce increases in [Ca2+]i in ovarian and breast cancer cells is likely to be due to an interaction with cell-surface receptors as the increases in [Ca2+]i were: (1) due to release of calcium from intracellular stores and not from transmembrane uptake due to changes in permeability; (2) blocked by lanthanum and suramin which do not enter cells; (3) blocked by phorbol esters which interrupt increases in [Ca2+]i induced through a number of different receptors; and (4) not detected in freshly isolated peripheral blood mononuclear cells, indicating cell type specificity. In addition, increases in [Ca2+]i induced by LPA, LPS and SPC in ovarian and breast cancer cells completely self-desensitized and cross-desensitized each other, but did not block increases in [Ca2+]i induced by thrombin. Lysophosphatidylglycerol (LPG), but not other lysophospholipids, inhibited LPA- but not LPS- or SPC-induced increases in [Ca2+]i, suggesting that LPA may interact with a different receptor(s) to LPS or SPC and that their downstream signalling pathways converge or interact. LPA, SPC and LPS also induced rapid increases in tyrosine phosphorylati...