Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, 21941-160 Rio de Janeiro, Brazil.
Cells. 2019 Jul 13;8(7):716. doi: 10.3390/cells8070716.
The establishment of prothrombotic states during cancer progression is well reported but the precise mechanisms underlying this process remain elusive. A number of studies have implicated the presence of the clotting initiator protein, tissue factor (TF), in circulating tumor-derived extracellular vesicles (EVs) with thrombotic manifestations in certain cancer types. Tumor cells, as well as tumor-derived EVs, may activate and promote platelet aggregation by TF-dependent and independent pathways. Cancer cells and their secreted EVs may also facilitate the formation of neutrophil extracellular traps (NETs), which may contribute to thrombus development. Alternatively, the presence of polyphosphate (polyP) in tumor-derived EVs may promote thrombosis through a TF-independent route. We conclude that the contribution of EVs to cancer coagulopathy is quite complex, in which one or more mechanisms may take place in a certain cancer type. In this context, strategies that could attenuate the crosstalk between the proposed pro-hemostatic routes could potentially reduce cancer-associated thrombosis.
在癌症进展过程中形成促血栓状态已有相关报道，但这一过程的确切机制仍难以捉摸。许多研究表明，凝血起始蛋白组织因子（TF）存在于某些癌症类型的循环肿瘤衍生细胞外囊泡（EVs）中，这些 EVs 与血栓表现有关。肿瘤细胞以及肿瘤衍生的 EVs 可能通过 TF 依赖和非依赖途径激活和促进血小板聚集。癌细胞及其分泌的 EVs 还可能促进中性粒细胞胞外诱捕网（NETs）的形成，这可能有助于血栓形成。或者，肿瘤衍生 EVs 中多聚磷酸盐（polyP）的存在可能通过 TF 非依赖途径促进血栓形成。我们得出结论，EVs 对癌症凝血功能障碍的贡献非常复杂，在某种癌症类型中可能存在一种或多种机制。在这种情况下，能够减弱所提出的促凝途径之间串扰的策略可能会降低与癌症相关的血栓形成。
