Formation of abnormal vasculature
The angiogenic switch induces abnormal vasculature
This image depicts normal versus tumour cell vasculature in simplified sketches (A), photographs of vasculature (B), and computerised 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 organised and the balance of pro- and anti-angiogenic factors is maintained. By contrast, tumour vasculature is tortuous and hyperpermeable, and the balance of pro- and anti-angiogenic factors favours neovascularisation.8
VEGF is a potent permeability 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 tumours, high levels of VEGF result in vasculature that is excessively permeable and leaky, leading to increased interstitial pressure within the tumour and uneven delivery of nutrients, oxygen and therapeutic agents to the tumour.7,67
Figure A: Reprinted by permission from Macmillan Publishers Ltd: Nat Med. 2001;7:987–9. © 2001. Figure B: Reprinted with permission from the American Association for Cancer Research. Tong RT, Boucher Y, Kozin S, et al. Cancer Res 2004;64:3731–6. 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 non-commercial 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.
Irregularities in tumour vasculature
The pathological beginnings of tumour vasculature are reflected in its abnormal phenotype. Whereas normal vasculature quickly matures and stabilises, tumour vasculature is characterised 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 favourable to tumour growth.7
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