Model depicting the molecular mediators of TCIPA/S induced by metastatic prostate cancer cells (PC3M). (A) The model shown depicts the activation pathway of key signaling molecules investigated in the present study. Pharmacologic inhibitors used to target receptors and signaling molecules in platelets are shown. The effects of these inhibitors are summarized by green symbols, which indicate inhibition of platelet aggregation only, or red symbols which indicate inhibition of both secretion and aggregation. (B) Hypothesized integrin α_IIbβ₃-FcγRIIa-P2Y₁₂ cross-talk following platelet exposure to PC3M cells. (1) Upon α_IIbβ₃ engagement an (2) “outside-in ” signal transduction is transmitted possibly triggering the (3-4) activation of an “inside-out” FcγRIIa-deriving downstream signaling with consequent release (5) of secondary mediators, such as ADP. ADP engagement of its cognate receptor P2Y₁₂ would result in the amplification of the response (6-7) converging in an augmented platelet aggregation.