Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Centro de Transplante de Medula Óssea, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Thromb Res. 2013 Oct;132(4):450-6. doi: 10.1016/j.thromres.2013.07.026. Epub 2013 Aug 3.
Coagulation proteins play a critical role in numerous aspects of tumor biology. Cancer cells express tissue factor (TF), the protein that initiates blood clotting, which frequently correlates with processes related to cell aggressiveness, including primary tumor growth, invasion, and metastasis. It has been demonstrated that TF gets incorporated into tumor-derived microvesicles (MVs), a process that has been correlated with cancer-associated thrombosis. Here, we describe the exchange of TF-bearing MVs between breast cancer cell lines with different aggressiveness potential. The highly invasive and metastatic MDA-MB-231 cells displayed higher surface levels of functional TF compared with the less aggressive MCF-7 cells. MVs derived from MDA-MB-231 cells were enriched in TF and accelerated plasma coagulation, but MCF-7 cell-derived MVs expressed very low levels of TF. Incubating MCF-7 cells with MDA-MB-231 MVs significantly increased the TF activity. This phenomenon was not observed upon pretreatment of MVs with anti-TF or annexin-V, which blocks phosphatidylserine sites on the surface of MVs. Our data indicated that TF-bearing MVs can be transferred between different populations of cancer cells and may therefore contribute to the propagation of a TF-related aggressive phenotype among heterogeneous subsets of cells in a tumor.
凝血蛋白在肿瘤生物学的众多方面发挥着关键作用。癌细胞表达组织因子（TF），即启动血液凝固的蛋白，这通常与细胞侵袭性相关的过程有关，包括原发性肿瘤生长、侵袭和转移。已经证明 TF 被整合到肿瘤衍生的微小泡（MVs）中，这一过程与癌症相关的血栓形成有关。在这里，我们描述了具有不同侵袭性潜力的乳腺癌细胞系之间 TF 携带的 MV 的交换。高度侵袭性和转移性的 MDA-MB-231 细胞表面的功能 TF 水平明显高于侵袭性较低的 MCF-7 细胞。源自 MDA-MB-231 细胞的 MV 富含 TF 并加速血浆凝固，但 MCF-7 细胞衍生的 MV 表达极低水平的 TF。用 MDA-MB-231 MV 孵育 MCF-7 细胞可显著增加 TF 活性。在用抗 TF 或 annexin-V 预处理 MV 时未观察到这种现象，抗 TF 或 annexin-V 可阻止 MV 表面的磷脂酰丝氨酸位点。我们的数据表明，TF 携带的 MV 可以在不同的癌细胞群体之间转移，因此可能有助于在肿瘤中细胞异质性亚群中传播与 TF 相关的侵袭表型。
