Expansion of myeloid immune suppressor Gr+CD11b+cells in tumor-bearing host directly promotes tumor angiogenesis
Expansion of myeloid immune suppressor Gr+CD11b+cells in tumor-bearing host directly promotes tumor angiogenesis
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DOI：
10.1016/j.ccr.2004.08.031
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发表时间：
2004-10-01
期刊：
影响因子：
50.3
通讯作者：
Lin, PC
中科院分区：
文献类型：
--
作者：
Yang, L;DeBusk, LM;Lin, PC
我们证明了髓系免疫抑制Gr+CD11b+细胞的一种新的肿瘤促进作用，这在癌症患者和荷瘤动物中是显而易见的。这些细胞约占肿瘤细胞总数的5%。与Gr+CD11b+细胞共注射的肿瘤表现出血管密度增加、血管成熟和坏死减少。这些免疫细胞产生高水平的MMP9。这些细胞中MMP9的缺失完全消除了它们的促肿瘤能力。Gr+CD11b+细胞也被发现直接掺入肿瘤内皮。与这一观察结果一致，Gr+ CD 11b+细胞在肿瘤微环境和促血管生成培养条件下获得了内皮细胞（EC）特性。我们的数据提供了证据表明，由肿瘤诱导的免疫源性Gr+CD11b+细胞通过产生MMP 9并分化为EC直接促进肿瘤生长和血管形成。
We demonstrate a novel tumor-promoting role of myeloid immune suppressor Gr+CD11b+ cells, which are evident in cancer patients and tumor-bearing animals. These cells constitute approximately 5% of total cells in tumors. Tumors coinjected with Gr+CD11b+ cells exhibited increased vascular density, vascular maturation, and decreased necrosis. These immune cells produce high levels of MMP9. Deletion of MMP9 in these cells completely abolishes their tumor-promoting ability. Gr+CD11b+ cells were also found to directly incorporate into tumor endothelium. Consistent with this observation, Gr+CD11b+ cells acquire endothelial cell (EC) properties in tumor microenvironment and proangiogenic culture conditions. Our data provide evidence that Gr+CD11b+ cells of immune origin induced by tumors directly contribute to tumor growth and vascularization by producing MMP9 and differentiating into ECs.