Figure 2.

Summary of coupling actions between blood platelets, ATX, LPA and LPA receptors in bone metastasis. Interaction of circulating tumour cells with platelets induces platelet aggregation and release of LPA through mechanisms involving phospholipases A1 and A2 (PLA_1/2) generating LPA directly or indirectly through synthesis of LPA precursors including LPC that was eventually degraded by ATX mobilized from the blood circulation or secreted by platelets. In the blood circulation, LPA will act on tumoural LPA₁ receptors promoting survival and invasion and potentially on platelet LPA₅ receptors promoting platelet aggregation. After colonizing the bone marrow, LPA will act on tumoural LPA₁ receptors promoting cell proliferation and pro‐osteoclastic cytokine (IL‐6, IL‐8) secretion promoting bone resorption indirectly or directly by acting on osteoclast LPA₁ receptors. LPA might act on megakaryocyte LPA₅ receptors to induce cell contraction. It is proposed that the pro‐metastatic action of LPA in bone metastasis might involve the action of LPA on megakaryocytes counteracting their negative action on osteoclast and tumour cells, blunting their protective action against bone metastasis progression. ?, requires experimental validation.