Role of nontumoral ATX derived from platelet α-granules in LPA production promoting bone metastasis of breast cancer cells. Interaction of CTCs with platelets induces the generation of LPA through the secretion of LPA and LPA precursors involving phospholipase A1/A2 activities and lysopholipase D activity of ATX released from α-granules.³⁹  Then, LPA promotes transendothelial cell migration and establishment of a disseminated tumor cell into the bone marrow.⁸¹  LPA enhances tumor cell proliferation and induces bone resorption through a direct action on osteoclasts⁵⁴  and indirectly throughout the secretion of anti-(GM-CSF) and pro-osteoclastic factors (IL-6, IL-8, GROα) that also act directly on osteoclasts or indirectly on osteoblasts by upregulating the release of the pro-osteoclastic factor RANKL.^38,53  Figure was generated using the database of images from Servier Medical Art from Servier (http://creativecommons.org/licenses/by/3.0/fr/).