Mature vasculature contains an endothelial cell lining with a surrounding sheath of pericytes/vascular smooth muscle cells (VSMCs).
Tumor vessels are immature and lack a pericyte sheath. Colocalization of
vascular endothelial growth factor receptor 2 (VEGFR-2) and
platelet-derived growth factor receptor beta (PDGF-Rβ) reduces pericyte ensheathment of
tumor vessels. We found that a 30%
dietary restriction (DR) enhanced vessel maturation in the mouse CT-2A
astrocytoma. DR reduced microvessel density and
VEGF expression in the
astrocytoma, while increasing recruitment of pericytes, positive for alpha-smooth muscle actin (α-SMA). Moreover, DR reduced colocalization of VEGF-R2 and PDGF-Rβ, but did not reduce total PDGF-Rβ expression. These findings suggest that DR promoted vessel normalization by preventing
VEGF-induced inhibition of the PDGF signaling axis in pericytes. DR appears to shift the
tumor vasculature from a leaky immature state to a more mature state. We suggest that vessel normalization could improve delivery of therapeutic drugs to
brain tumors.