Milsom Chloe, Yu Joanne, May Linda, Magnus Nathalie, Rak Janusz
Henderson Research Centre, McMaster University, Hamilton, Ontario, Canada.
Semin Thromb Hemost. 2008 Mar;34(2):170-81. doi: 10.1055/s-2008-1079257.
Oncogenic upregulation of tissue factor (TF) and release of TF-containing microvesicles play an important role in cancer-related coagulopathy (Trousseau's syndrome), angiogenesis, and disease progression. In addition, certain types of host cells (stromal cells, inflammatory cells, activated endothelium) may also express TF. Although the relative contribution of host-related versus tumor-related TF to tumor progression is not known, our recent studies indicate that the role of both sources of TF in tumor formation is complex and context-dependent. Disruption of TF expression/activity in cancer cells leads to tumor growth inhibition in immunodeficient mice, even in cases where TF overexpression is driven by potent oncogenes ( K-RAS or EGFR). Interestingly, TF expression in vivo appears to be influenced by many factors, including the level of oncogenic transformation, tumor microenvironment, and differentiation from cancer stem-like cells. We postulate that activation of TF signaling and coagulation may deliver growth-promoting stimuli (e.g., fibrin, thrombin, platelets) to dormant cancer stem cells (CSCs). Functionally, these influences may be tantamount to formation of a provisional (TF-dependent) cancer stem cell niche. As such, these changes may contribute to the involvement of CSCs in tumor growth, angiogenesis, and metastasis.
组织因子（TF）的致癌性上调以及含TF微泡的释放，在癌症相关凝血病（特鲁索综合征）、血管生成和疾病进展中发挥重要作用。此外，某些类型的宿主细胞（基质细胞、炎性细胞、活化内皮细胞）也可能表达TF。虽然宿主相关TF与肿瘤相关TF对肿瘤进展的相对贡献尚不清楚，但我们最近的研究表明，两种来源的TF在肿瘤形成中的作用是复杂的且取决于具体情况。在免疫缺陷小鼠中，癌细胞中TF表达/活性的破坏会导致肿瘤生长受到抑制，即使在TF过表达由强效致癌基因（K-RAS或EGFR）驱动的情况下也是如此。有趣的是，TF在体内的表达似乎受多种因素影响，包括致癌转化水平、肿瘤微环境以及癌干细胞样细胞的分化。我们推测，TF信号传导和凝血的激活可能会将促生长刺激（如纤维蛋白、凝血酶、血小板）传递给休眠的癌干细胞（CSC）。从功能上讲，这些影响可能等同于形成一个临时的（TF依赖的）癌干细胞龛。因此，这些变化可能促使癌干细胞参与肿瘤生长、血管生成和转移。
