Fig. 1.

Schematic representation of tumor-mediated education of platelets and the megakaryocyte leading to metastasis. (a) Megakaryocytes in the bone marrow and lungs sort specific RNA and proteins into platelet precursors. (b) Circulating platelets contain a variety of RNA transcripts and proteins. During their 7–10-day lifespan, platelets interact with immune cells, cancer cells, and stromal cells. These direct interactions as well as distant cell signaling, for instance, via vesicle-mediated communication in whole blood, changes the content of the platelet and platelet function. (c) This process leads to the development of tumor-educated platelets. Next, tumor-educated platelets can influence the process of metastasis formation by stimulating or blocking immune cells, endothelial cells, stromal cells, and cancer cells, either by direct cell-to-cell contact or by releasing extracellular queues. (d) Finally, metastasis could affect the sorting of specific RNA and proteins of megakaryocytes into platelets