Tumor-Derived Tissue Factor Aberrantly Activates Complement and Facilitates Lung Tumor Progression via Recruitment of Myeloid-Derived Suppressor Cells.
Tumor-Derived Tissue Factor Aberrantly Activates Complement and Facilitates Lung Tumor Progression via Recruitment of Myeloid-Derived Suppressor Cells.
复制标题
肿瘤源性组织因子异常激活补体并通过招募骨髓源性抑制细胞促进肺肿瘤进展。
DOI：
10.3390/ijms18010022
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发表时间：
2017-01-19
影响因子：
5.6
通讯作者：
Zhu B
中科院分区：
文献类型：
--
作者：
Han X;Zha H;Yang F;Guo B;Zhu B
组织因子（TF）是外源性凝血的起始因子，它的非凝血异构体选择性剪接的TF（asTF）与肿瘤的发生发展密切相关。在肿瘤微环境中，TF诱导的凝血在肿瘤进展中的作用仍有待充分阐明。使用TF敲低的肺肿瘤细胞，我们表明TF是促凝血活性的主要成分，但在肿瘤细胞的细胞生物学中是不稳定的。在异种移植模型中，使用肿瘤微环境的免疫组织化学分析和流式细胞术分析，我们证明TF诱导的纤维蛋白沉积与补体激活和髓源性抑制细胞（MDSC）募集相关，与肿瘤进展呈正相关。C5aR拮抗作用减弱了TF对肿瘤进展的作用，并减少了MDSC的募集。总之，我们的数据表明，在肿瘤微环境中，TF诱导的凝血激活补体系统，随后招募骨髓来源的抑制细胞以促进肿瘤生长，这为肿瘤微环境中肿瘤进展过程中凝血诱导的补体激活带来了新的见解。
The initiator of extrinsic coagulation, tissue factor (TF), and its non-coagulant isoform alternatively spliced TF (asTF) are closely associated with tumor development. In the tumor microenvironment, the role of TF-induced coagulation in tumor progression remains to be fully elucidated. Using TF-knockdown lung tumor cells, we showed that TF is the dominant component of procoagulant activity but is dispensable in the cellular biology of tumor cells. In a xenograft model, using immunohistochemical analysis and flow cytometry analysis of the tumor microenvironment, we demonstrated that TF-induced fibrin deposition, which is correlated with complement activation and myeloid-derived suppressor cell (MDSC) recruitment, is positively associated with tumor progression. C5aR antagonism blunted the effect of TF on tumor progression and decreased MDSC recruitment. In conclusion, our data suggested that in tumor microenvironment, TF-induced coagulation activated the complement system and subsequently recruited myeloid-derived suppressor cells to promote tumor growth, which brings new insights into the coagulation-induced complement activation within the tumor microenvironment during tumor progression.