Interleukin-6 Stimulates Defective Angiogenesis.
Interleukin-6 Stimulates Defective Angiogenesis.
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DOI：
10.1158/0008-5472.can-15-1227
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发表时间：
2015-08-01
期刊：
影响因子：
11.2
通讯作者：
Balkwill F
中科院分区：
文献类型：
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作者：
Gopinathan G;Milagre C;Pearce OM;Reynolds LE;Hodivala-Dilke K;Leinster DA;Zhong H;Hollingsworth RE;Thompson R;Whiteford JR;Balkwill F
细胞因子白细胞介素-6（IL-6）在人类和实验性癌症中具有许多促肿瘤活性，但其作为血管生成剂的潜力尚未得到充分研究。在这里，我们表明，IL-6可以直接诱导血管发芽在离体主动脉环模型，以及内皮细胞增殖和迁移，具有类似的效力VEGF。然而，IL-6刺激的主动脉环血管芽有缺陷的周细胞覆盖相比，VEGF刺激的血管。IL-6作用于周细胞的机制涉及Notch配体Jagged 1以及血管生成素2（Ang 2）的刺激。当卵巢癌的腹膜异种移植物用抗IL-6抗体处理时，血管的周细胞覆盖恢复。此外，在人类卵巢癌活检中，IL-6 mRNA、Jagged 1和Ang 2的水平之间存在关联。我们的研究结果对靶向VEGF或IL-6的癌症治疗的使用以及理解癌症，慢性炎症性疾病和中风中的异常血管生成具有意义。
The cytokine interleukin-6 (IL-6) has a number of tumor-promoting activities in human and experimental cancers, but its potential as an angiogenic agent has not been fully investigated. Here we show that IL-6 can directly induce vessel sprouting in the ex vivo aortic ring model, as well as endothelial cell proliferation and migration, with similar potency to VEGF. However, IL-6-stimulated aortic ring vessel sprouts had defective pericyte coverage compared to VEGF-stimulated vessels. The mechanism of IL-6 action on pericytes involved stimulation of the Notch ligand Jagged1 as well as Angiopoietin2 (Ang2). When peritoneal xenografts of ovarian cancer were treated with an anti-IL-6 antibody, pericyte coverage of vessels was restored. In addition, in human ovarian cancer biopsies there was an association between levels of IL-6mRNA, Jagged1 and Ang2. Our findings have implications for the use of cancer therapies that target VEGF or IL-6 and for understanding abnormal angiogenesis in cancers, chronic inflammatory disease and stroke.