The role of tumor-platelet interplay and micro tumor thrombi during hematogenous tumor metastasis.

Abstract

In addition to their pivotal roles in coagulation and thrombosis, platelets are crucial in tumor progression, with plenty of clinical and experimental data demonstrating that the interplay of platelets and tumor cells is essential for hematogenous tumor metastasis. After detach from primary sites, tumor cells intravasate into the blood circulation becoming circulating tumor cells and induce platelet activation, aggregation and encasement around tumor cells to form micro tumor thrombi, which create a permissive tumor microenvironment for metastasis. Platelets in micro tumor thrombi protect tumor cells from immune surveillance and anoikis (detachment-triggered apoptosis) through various pathways, which are significant for tumor cell survival in the bloodstream. Moreover, platelets can facilitate tumor metastasis by expediting epithelial-mesenchymal transition (EMT), adhesion to the endothelium, angiogenesis, tumor proliferation processes and platelet-derived microvesicle (PMV) formation. Here, we provide a synopsis of the current understanding of the formation of micro tumor thrombi and the role of micro tumor thrombi in tumor hematogenous metastasis based on the tumor-platelet interplay. We also highlight potential therapeutic strategies targeting platelets for tumor treatment, including cancer-associated platelet-targeted nanomedicines.