Background: It is well accepted that the bidirectional crosstalk between platelets and cancer cells promotes tumorigenesis and metastasis. In an early step, cancer cells trigger platelet granule and extracellular vesicle release that is needed to facilitate cancer cell survival in circulation.
Objectives: To discover the early crosstalk of cancer cells and platelets.
Methods: Cancer cells were incubated with freshly isolated and stained human platelets. Confocal laser scanning microscopy and flow cytometry was used to visualize and to quantify platelet uptake and the membrane presence of CD42 on cancer cells. Dyngo4a was used to test if platelet uptake is a dynamin-dependent process.
Results: We found a dynamin-dependent uptake of platelets by cancer cells. This is followed by the recycling of the platelet-specific protein CD42a and its incorporation into cancer cells' plasma membrane, which is not a result of platelet RNA transfer by platelet-derived microparticles and exosomes. Time course of platelet uptake follows a sigmoid function revealing that 50% of the cancer cells are positive for platelets after approximately 38 min. Platelet uptake was observed for the tested cancerous cells (A549, MCF-7, and MV3) but not for the non-cancerous cell line 16HBE14o-.
Conclusions: Our results demonstrate that cancer cells hijack platelets by phagocytosis and recycling of platelet membrane proteins. The uptake of platelets has additional advantages for cancer cells: access to the entire and undiluted platelet proteome, transcriptome, and secretome. These novel findings will allow further mechanistic elucidation and thus help us gain deeper insights into platelet-assisted hematogenous metastasis.
Keywords: dynamin; flow cytometry; metastasis; phagocytosis; recycling.
© 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.