Enlarged vessels (green) form in the presence of MMP-cleaved forms of VEGF.

VEGF stuck to the extracellular matrix induces branchy vessels that support tumorigenesis, but soluble VEGF prompts wider vessels that cannot provide for a tumor, as shown on page 681 by Lee et al.

VEGF directs vascular growth and patterning in developing, adult, and tumor tissues. This extracellular signaling is thought to require VEGF that is not bound to the matrix. Soluble VEGF is made by either mRNA splicing that removes the matrix attachment region, or by MMP-dependent matrix remodeling. Lee et al. now show that several MMPs also cleave VEGF directly, thus releasing it from the matrix.Contrary to expectations, however, soluble VEGF was less effective than its matrix-bound version at supporting the vessel growth needed for tumor survival. Uncleaved VEGF induced long, thin, branchy vessels that provided the circulation needed for tumorigeneis. But...

The Rockefeller University Press
2005
The Rockefeller University Press
2005
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