Platelets facilitate metastasis through multiple mechanisms. (A) Tumor cells induce platelet aggregation and embolus formation, which can enhance survival in the stressful milieu of the circulation. This includes protection from immune-mediated clearance (I) and from shear stresses that are toxic to tumor cells (II). (B) Platelets also form complexes with leukocytes and facilitate adhesion to endothelial cells (III). It is hypothesized that this adhesive cellular aggregate is competent to extravasate into the secondary site of metastasis. Numerous platelet-derived factors enhance angiogenesis (IV), growth, and tissue-specific modulation of the new microenvironment. One of these factors is LPA, which acts as a direct tumor cell mitogen (V) and as an enhancer of osteolysis through induction of IL-6 and IL-8 by cancer cells in the bone marrow (VI).