Schematic representation of LPA-dependent platelet-induced tumor cell metastasis. Tumor cell-induced platelet production of bioactive LPA (inhibitor: LPA receptor antagonist Ki16425) requires a first step of platelet aggregation that is prevented by selective inhibitors of α_IIbβ₃ integrin (RGDS, ReoPro), adenosine 5′-diphosphate activating pathway (Apyrase), and P2Y12 inhibitor (Clopidogrel). The second step requires the activation of phospholipases A1 and A2 (inhibitor: Palmostatin B) degrading membrane phospholipids among direct (phosphatidic acid) or indirect (phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine) precursors of LPA (LPC, lysophosphatidylserine, and lysophosphatidylethanolamine), that in turn are hydrolyzed by ATX/LysoPLD (ATX; lysoPLD inhibitors: BMP22 en PF-8380), released by activated platelets acting as free enzymes and/or bound to β₃ integrins (α_IIbβ₃ and α_Vβ₃). LPE, lysophosphatidylethanolamine; LPS, lysophosphatidyserine; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PLA1, phospholipase A1; PLA2, phospholipase A2; PS, phosphatidylserine.