Interleukin-17 promotes angiogenesis and tumor growth
Interleukin-17 promotes angiogenesis and tumor growth
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DOI：
10.1182/blood-2002-05-1461
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发表时间：
2003-04-01
期刊：
影响因子：
20.3
通讯作者：
Lotze, MT
中科院分区：
文献类型：
--
作者：
Numasaki, M;Fukushi, J;Lotze, MT
白细胞介素-117 （IL-17）是CD4 t细胞衍生的促炎细胞因子。我们研究了肿瘤局部产生的IL-17的影响，作为评估其生物学功能的一种手段。虽然重组IL-17蛋白或IL-17基因逆转录病毒转导入肿瘤不影响体外增殖，但与对照组相比，IL-17转染物在体内的生长速度更快。因子VIII免疫染色显示，与对照组相比，用IL-17转导的肿瘤血管密度显著增加。IL-17确实诱导了大鼠角膜新生血管的形成。此外，通过中和IL-17单克隆抗体，CD4 T细胞条件培养基中的血管生成活性明显受到抑制。IL-17对血管内皮细胞的生长无直接影响，而IL-17对血管内皮细胞的迁移有明显的促进作用。IL-17还能显著促进血管内皮细胞的脐带形成。此外，IL-17上调成纤维细胞和肿瘤细胞对多种促血管生成因子的表达。这些发现揭示了IL-17作为CD4 t细胞衍生的血管生成介质的新作用，刺激血管内皮细胞迁移和脐带形成，并调节多种促血管生成因子的产生。此外，他们认为抑制IL-17的生物作用可能对血管生成相关疾病有治疗益处。
Interleukin-117 (IL-17) is a CD4 T-cell-derived proinflammatory cytokine. We investigated the effects of locally produced IL-17 by tumors as a means to evaluate its biologic function. Although recombinant IL-17 protein or retroviral transduction of IL-17 gene into tumors did not affect in vitro proliferation, IL-17 transfectants grew more rapidly in vivo when compared with controls. Immunostaining for Factor VIII revealed that tumors transduced with IL-17 had significantly higher vascular density when compared with controls. IL-17 indeed elicited neovascularization in rat cornea. In addition, angiogenic activity present in the conditioned media of CD4 T cells was markedly suppressed by neutralizing monoclonal antibody to IL-17. IL-17 had no direct effect on the growth of vascular endothelial cells, whereas IL-17 significantly stimulated migration. IL-17 also markedly promoted the cord formation of vascular endothelial cells. In addition, IL-17 up-regulated elaboration of a variety of proangiogenic factors by fibroblasts as well as tumor cells. These findings reveal a novel role for IL-17 as a CD4 T-cell-derived mediator of angiogenesis that stimulates vascular endothelial cell migration and cord formation and regulates production of a variety of proangiogenic factors. Furthermore, they suggest that inhibition of biologic action of IL-17 May have therapeutic benefits when applied to angiogenesis-related disorders.