Lysophospholipids activate ovarian and breast cancer cells

摘要: We have investigated the effects of phospholipids on activation and proliferation ovarian breast cancer cells. Lysophosphatidic acid (LPA), lysophosphatidylserine (LPS) sphingosylphosphorylcholine (SPC) all induce transient increases in cytosolic free Ca2+ ([Ca2+]i) both cell lines. The ability LPA, LPS SPC to [Ca2+]i cells is likely be due an interaction with cell-surface receptors as were: (1) release calcium from intracellular stores not transmembrane uptake changes permeability; (2) blocked by lanthanum suramin which do enter cells; (3) phorbol esters interrupt induced through a number different receptors; (4) detected freshly isolated peripheral blood mononuclear cells, indicating type specificity. In addition, completely self-desensitized cross-desensitized each other, but did block thrombin. Lysophosphatidylglycerol (LPG), other lysophospholipids, inhibited LPA- LPS- or SPC-induced [Ca2+]i, suggesting that LPA may interact receptor(s) their downstream signalling pathways converge interact. also rapid tyrosine phosphorylation specific cellular proteins, including p125FAK. Strikingly, SPC, mitogen-activated protein (MAP) kinases. Despite activate similar signaling events, exhibited markedly proliferation. Whereas significant increase proliferation, substantially alter Surprisingly, phosphatidic (PA), p125FAK MAP kinases, albeit at higher concentrations LPA. discordance between sensitivity LPG, early biochemical events stimulated, eventual response combine suggest probably utilizes receptor LPS, PA. Therefore are sensitive play role growth these tumour patient thus potential targets for therapy.