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Cancers 2017, 9(8), 97; https://doi.org/10.3390/cancers9080097

Localization of VEGF to Vascular ECM Is an Important Aspect of Tumor Angiogenesis

1
ABL Bio Inc., Gyeonggi-Do 13488, Korea
2
Tumor Microenvironment and Cancer Immunology Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Samuel C. Mok
Received: 23 June 2017 / Revised: 22 July 2017 / Accepted: 26 July 2017 / Published: 28 July 2017
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Abstract

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. View Full-Text
Keywords: VEGF; vascular basement membrane; tumor vascularization; vessel diameter; vascular function; hypoxia; pericytes; endothelial cells; macrophages; invadopodia VEGF; vascular basement membrane; tumor vascularization; vessel diameter; vascular function; hypoxia; pericytes; endothelial cells; macrophages; invadopodia
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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You, W.-K.; Stallcup, W.B. Localization of VEGF to Vascular ECM Is an Important Aspect of Tumor Angiogenesis. Cancers 2017, 9, 97.

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