Schematic representation of LPA/autotaxin effects on the progression of osteolytic bone metastases.

<p>Bone-residing breast cancer cells (1) induce platelet (2) aggregation and the release of LPA and LPA precursors (LPC) from activated platelets. Platelet-derived LPA and LPA-derived from autotaxin (ATX) lysoPLD activity secreted by cancer cells can act on tumor cells to stimulate both tumor growth and the production of IL-6 and IL-8, which in turn induce the expression of RANK-L by osteoblasts (3) that stimulate osteoclast precursors (4) differentiation and osteoclast-mediated bone resorption. Platelet-derived LPA and LPA derived from ATX activity can act directly on osteoblasts to stimulate migration and proliferation, and on osteoclast precursors to stimulate osteoclastogenesis. Doted arrows indicate unknown origin.