Tumor-Educated Platelet Extracellular Vesicles: Proteomic Profiling and Crosstalk with Colorectal Cancer Cells

Background: Platelet-cancer cell interactions modulate tumor metastasis and thrombosis in can-cer. Platelet-derived extracellular vesicles(EVs) can contribute to these outcomes. Methods: We characterized the medium-size EVs(mEVs) released by thrombin-stimulated platelets of colo-rectal cancer(CRC) patients and healthy subjects(HS) on the capacity to induce epitheli-al-mesenchymal transition(EMT)-related genes and cyclooxygenase(COX)-2(PTGS2), and thromboxane(TX)B2 production in cocultures with four colorectal cancer cell lines. Plate-let-derived mEVs were assessed for their size distribution and proteomics signature. Re-sults: The mEV population released from thrombin-activated platelets of CRC patients had a different size distribution vs. HS. Platelet-derived mEVs from CRC patients, but not from HS, upregulated EMT marker genes, such as TWIST1 and VIM, and downregulated CDH1. PTGS2 was also upregulated. In cocultures of platelet-derived mEVs with cancer cells, TXB2 generation was enhanced. The proteomics profile of mEVs released from activated platelets of CRC patients re-vealed that 119 proteins were downregulated and 89 upregulated vs. HS. Conclusions: We show that mEVs released from thrombin-activated platelets of CRC patients have distinct features (size distribution and proteomics cargo) vs. HS and promote prometastatic and prothrombotic phenotypes in cancer cells. The analysis of platelet-derived mEVs from CRC patients could pro-vide valuable information for developing an appropriate treatment plan.