Despite the notion that platelets can promote tumor metastatization dates back to the 19th century , the underlying mechanisms have remained elusive. Two hypothesis have been proposed to explain plateletfacilitated tumor spreading: 1) a pro-angiogenic activity of platelet-derived cytokines, and 2) a protective effect of the platelet cot that shields tumor cells from both immune cell aggression and shear stress . In this issue, Elena Adinolfi discusses two recently published papers, one in Cancer Cell and the second one in Carcinogenesis, which highlight the involvement of nucleotides in platelet-mediated transmigration of tumor cells through vascular endothelia (Highlight N. 1) and the central role of the P2X7 receptor in cancer metastatization (Highlight N. 2). Globally, these papers testify the continued interest in unfolding the involvement of the purinergic system in cancer dissemination and support the development of novel purinergic-based potent and effective drugs for the treatment of cancer
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