VEGF not always a pro-cancer molecule

NEW YORK (Reuters Health) - Vascular endothelial growth factor (VEGF) is usually thought of as a molecule that promotes cancer growth by increasing angiogenesis, but findings from two studies, reported in the November 9th online issue of Nature, suggest that in some circumstance, VEGF may suppress tumor growth.

The revelation that VEGF's actions are more complex than originally thought could have important implications for treatments that target this molecule.

"The take-home message could be that anti-angiogenesis approaches need to be evaluated carefully, and potentially in the context of tumor inflammation. And that tumor vascularization is a more complicated matter than the simple equation of more vessels equals bigger tumor, fewer vessels equals tumor reduction." Dr. Randall Johnson, senior author of one of the studies, told Reuters Health.

According to Dr. Johnson, a researcher with the University of California, San Diego, his team's study is not the first to look at the effects of VEGF inhibition. However, in previous studies VEGF action was either inhibited globally or only in malignant cells. "This is the first study to remove VEGF secretion specifically and solely from inflammatory cells."

Using murine models, the investigators found that the chaotic, leaky vessels typically found in solid tumors are the result of inflammatory cell VEGF and not VEGF produced by the malignant cells. When production of inflammatory cell VEGF was blocked, the tumors actually grew and progressed more rapidly.

"This latter finding was really a shock to us, and indicated that VEGF expression and its effects on tumors is much more complex then we realized," Dr. Johnson said.

In the second study, which was conducted by many of the same researchers from the first, VEGF was found to be a negative regulator of vascular smooth muscle cells and vessel maturation.

The results, senior author Dr. David A. Cheresh, from UCSD, notes, confirm that VEGF expression does induce endothelial cell proliferation and migration. However, in the context of platelet-derived growth factor-mediated angiogenesis, VEGF disrupts vascular smooth muscle cell coverage of vascular sprouts, which destabilizes the vessel.

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