Impact of VEGF on glioblastoma microvasculature

VEGF has been proven to increase vascular permeability by inducing the formation of structural abnormalities, including fenestrations, open gaps, and clustered and fused caveolae in the endothelium. In a study by Robert et al, tumors implanted in subcutaneous (SC) tissue vs intracerebral (IC) tissue were examined to see if the host microvasculature determines the morphology and therefore the function of the tumor vasculature or if VEGF overrides all host microvascular endothelial input.¹

The study revealed that when tumors were implanted in IC tissue, the microvasculature underwent a remarkable transformation in both structure (increase in endothelial gaps and fenestrations) and function (increase in permeability). Additionally, while the tumors produced similar amounts of VEGF in the 2 conditions, the expression of VEGF receptors was increased in the IC tissue.¹

Electron micrographs of vessels in the normal brain (A), VEGF:Chinese hamster ovary (CHO) (B), and M1S (C) tumors growing in the brain. An extensive electron-dense endothelial junction is common to normal brain vessels (A, j). This junction is drastically compromised in tumor vessels, in which the intercellular gaps can be as large as 260 nm (B and C, asterisks). VEGF:CHO tumors had numerous gaps (B, asterisks), which may be remnants of fenestrations (arrowheads). B: Boxed areas are shown as insets. Bars (A, B, insets, and C), 500 nm.¹

Reprinted from Am J Pathol 1998, 153:1239-1248 with permission from the American Society for Investigative Pathology.

The authors conclude that these results indicate there is a drastic difference in neovasculature of identical tumor types when they are grown in different locations. These findings are important, as the differences in tumor vessel morphology affect tumor permeability.¹

Reference:

1.

Roberts W, Delaat J, Nagane M, et al. Am J Path. 1998;153(4):1239-1248.