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Formation of abnormal vasculature

The angiogenic switch induces abnormal vasculature

This image depicts normal vs tumor cell vasculature in simplified sketches (A), photographs of vasculature (B), and computerized renderings (C). (D) shows the balance of pro- and anti-angiogenic factors in normal and abnormal vasculature. Note that under normal conditions, the vasculature is well organized, and the balance of pro- and anti-angiogenic factors is maintained. By contrast, tumor vasculature is tortuous and hyperpermeable, and the balance of pro- and anti-angiogenic factors favors neovascularization.¹

Figure A: Reprinted by permission from Macmillan Publishers Ltd: Nat Med. 2001;7:987-989. © 2001. Figure B: Reprinted with permission from the American Association for Cancer Research. Tong RT, Boucher Y, Kozin S, et al. Cancer Res. 2004;64:3731-3736. Figures C and D: From Jain RK. Science. 2005;307:58-62. Reprinted with permission from AAAS. Readers may view, browse, and/or download material for temporary copying purposes only, provided these uses are for noncommercial personal purposes. Except as provided by law, this material may not be further reproduced, distributed, transmitted, modified, adapted, performed, displayed, published, or sold in whole or part, without prior written permission from the publisher.

VEGF is a potent permeability factor

Vascular endothelial growth factor (VEGF) stimulates vascular permeability in small blood vessels. The increased permeability causes the leakage of plasma proteins and the formation of an extravascular fibrin gel, providing a suitable environment for endothelial cell growth. In tumors, high levels of VEGF result in vasculature that is excessively permeable and leaky, leading to increased interstitial pressure within the tumor and uneven delivery of nutrients, oxygen, and therapeutic agents to the tumor.^2,3

Irregularities in tumor vasculature

The pathologic beginnings of tumor vasculature are reflected in its abnormal phenotype. Whereas normal vasculature quickly matures and stabilizes, tumor vasculature is characterized by structural and functional abnormalities. These defects, due in large part to VEGF, include tortuousness, hyperpermeability, and lack of structure-giving pericytes. Together, these abnormalities create an environment that is favorable to tumor growth.²

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References:

1.

Jain RK. Science. 2005;307:58-62.

2.

Jain RK. Nat Med. 2001;7:987-989.

3.

Dvorak HF, Brown LF, Detmar M, et al. Am J Pathol. 1995;146:1029-1039.