Platelets Lead Morphological, Phenotypic and Functional Changes in Tumor Cells.

Abstract

BackgroundPlatelets are active players in tumorigenesis, although the exact interactive mechanisms and their direct impact on tumor cells remain largely unknown. MethodsBidirectional transference of lipids, proteins and RNA between platelets and tumor cells and its impact on tumor cell behavior and tumor process are analyzed in this work. Phenotypic, genetic and functional modifications induced by platelets were analyzed both in tumor cell lines and in circulating tumor cells (CTCs). ResultsBesides cross-talk between platelets and tumor cells, we demonstrated an efficient exchange of lipids, proteins and RNA. Remarkably, we observed that platelets transferred structural components to tumor cells with higher efficiency than tumor cells to platelets (p=0.001). This biological interplay occurred by direct contact, internalization or via extracellular vesicles. As a result, tumor cells acquired platelet markers (CD61 and CD42), showed decreased EpCAM, expressed epithelial-to-mesenchymal transition markers, and increased proliferation rates. Analysis of platelets marker CD61 in CTCs showed intra and inter patient heterogeneity.ConclusionsOur results demonstrated, for the first time, that platelets educate tumor cells by highly efficient transference of lipids, proteins and RNA through different mechanisms. These results suggest that tumor cells and CTCs might acquire highly dynamic and aggressive phenotypes due to platelets interaction including EMT, stem-like phenotype and high proliferative rates.

Advances in circulating tumor cells for early detection, prognosis and metastasis reduction in lung cancer

“…The research results of Alba et al demonstrated for the first time that platelets not only indirectly activate pathways related to the microenvironment, but also efficiently convey lipids, proteins and RNA via various mechanisms to educate tumor cells. The interaction with platelets may lead to tumor cells and CTCs adopting highly dynamic and aggressive traits, which can involve EMT, stem cell-like phenotype, and elevated proliferative capacities (122).…”