Localization of VEGF to Vascular ECM Is an Important Aspect of Tumor Angiogenesis.
Localization of VEGF to Vascular ECM Is an Important Aspect of Tumor Angiogenesis.
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VEGF将VEGF定位到血管ECM是肿瘤血管生成的重要方面。
DOI：
10.3390/cancers9080097
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发表时间：
2017-07-28
期刊：
影响因子：
5.2
通讯作者：
Stallcup WB
中科院分区：
文献类型：
--
作者：
You WK;Stallcup WB
我们的研究已经确定了几个例子，其中VEGF-A与缺乏血管的细胞外基质结合减少导致肿瘤血管化和肿瘤生长缺陷：(1)颅内B16F10黑色素瘤基质中胶原VI的种系消融；(2) MDA-MB-231乳腺肿瘤细胞中Tks5支架蛋白的敲低；(3) MMTV-PyMT乳腺肿瘤间质中NG2蛋白多糖的种系消融；(4)颅内B16F10黑色素瘤基质中NG2的骨髓特异性消融。在四种类型的实验小鼠中，肿瘤缺氧均增加，并伴有总VEGF-A的增加。然而，尽管VEGF-A在对照小鼠中与肿瘤血管高度相关，但在所有四组实验小鼠中，VEGF-A在肿瘤中的弥散分布要广泛得多，可能是由于血管细胞外基质的程度减少。在失去VEGF-A定位的同时，每种情况下的肿瘤血管都比对照小鼠的肿瘤血管直径更小，渗漏更大。由于血管功能差，肿瘤生长减少。观察到的血管变化发生在没有血管密度改变的情况下，这一事实表明，在了解血管生成在肿瘤进展中的重要性方面，血管结构和功能的检查比血管密度的检查更有用。
Our research has identified several examples in which reduced VEGF-A binding to deficient vascular extracellular matrix leads to deficits in tumor vascularization and tumor growth: (1) germline ablation of collagen VI in the stroma of intracranial B16F10 melanomas; (2) knockdown of the Tks5 scaffolding protein in MDA-MB-231 mammary tumor cells; (3) germline ablation of NG2 proteoglycan in the stroma of MMTV-PyMT mammary tumors; and (4) myeloid-specific ablation of NG2 in the stroma of intracranial B16F10 melanomas. Tumor hypoxia is increased in each of the four types of experimental mice, accompanied by increases in total VEGF-A. However, while VEGF-A is highly associated with tumor blood vessels in control mice, it is much more diffusely distributed in tumors in all four sets of experimental mice, likely due to reduced extent of the vascular extracellular matrix. In parallel to lost VEGF-A localization, tumor vessels in each case have smaller diameters and are leakier than tumor vessels in control mice. Tumor growth is decreased as a result of this poor vascular function. The fact that the observed vascular changes occur in the absence of alterations in vascular density suggests that examination of vessel structure and function is more useful than vascular density for understanding the importance of angiogenesis in tumor progression.
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DOI：
10.1038/newbio242148a0
发表时间：
1973-01-01
期刊：
NATURE-NEW BIOLOGY
影响因子：
--
作者：
FIDLER, IJ
通讯作者：
FIDLER, IJ
影响因子：
3.3
作者：
Ferrara N
通讯作者：
Ferrara N
影响因子：
6.6
作者：
Blouw, Barbara;Seals, Darren F.;Courtneidge, Sara A.
通讯作者：
Courtneidge, Sara A.
影响因子：
3.5
作者：
Bonaldo, P;Braghetta, P;Bressan, GM
通讯作者：
Bressan, GM
DOI：
10.1161/atvbaha.108.179663
发表时间：
2009-06-01
影响因子：
8.7
作者：
Ferrara, Napoleone
通讯作者：
Ferrara, Napoleone