Endothelial Cords Promote Tumor Initial Growth prior to Vascular Function through a Paracrine Mechanism.
Endothelial Cords Promote Tumor Initial Growth prior to Vascular Function through a Paracrine Mechanism.
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内皮索通过旁分泌机制促进肿瘤在血管功能之前的初始生长
DOI：
10.1038/srep19404
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发表时间：
2016-01-14
影响因子：
4.6
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Zhao C;Zhang W;Zhao Y;Yang Y;Luo H;Ji G;Dong E;Deng H;Lin S;Wei Y;Yang H
血管生成开关是一个重要的致癌步骤，决定是否微小肿瘤保持休眠或进一步发展。一般认为，这种肿瘤发生的主要功能是通过血液循环提供氧气和营养物质。利用斑马鱼和小鼠肿瘤模型的体内成像，我们发现内皮索积极地渗透到微肿瘤中，并在接受血管血液灌注前保持非循环状态数天。出乎意料的是，我们发现，如果通过阻断VEGF-VEGFR 2信号传导或使用血管缺陷斑马鱼突变体去除内皮索，则两种模型中的初始肿瘤生长显著减少。进一步表明，由内皮细胞（EC）分泌的包括IL-8在内的可溶性因子负责刺激肿瘤细胞增殖。这些发现证实了肿瘤血管生成在促进肿瘤生长中起着更早和更广泛的作用，这与血管循环无关。了解血管生成肿瘤进展的这种新机制为癌症治疗提供了新的切入点。
The angiogenic switch is an important oncogenic step that determines whether microtumors remain dormant or progresses further. It has been generally perceived that the primary function of this tumorgenic event is to supply oxygen and nutrients through blood circulation. Usingin vivoimaging of zebrafish and mouse tumor models, we showed that endothelial cords aggressively penetrated into microtumors and remained non-circulatory for several days before undergoing vascular blood perfusion. Unexpectedly, we found that initial tumor growth in both models was significantly reduced if endothelial cords were removed by blocking VEGF-VEGFR2 signaling or using a vascular deficient zebrafish mutant. It was further shown that soluble factors including IL-8, secreted by endothelial cells (ECs) were responsible for stimulating tumor cells proliferation. These findings establish that tumor angiogenesis play a much earlier and broader role in promoting tumor growth, which is independent of vascular circulation. Understanding this novel mechanism of angiogenic tumor progression offers new entry points for cancer therapeutics.