dietary restriction promotes vessel maturation in a mouse astrocytoma饮食限制促进血管成熟在鼠标星形细胞瘤.pdfVIP

Hindawi Publishing Corporation Journal of Oncology Volume 2012, Article ID 264039, 10 pages doi:10.1155/2012/264039 Research Article Dietary Restriction Promotes Vessel Maturation in a Mouse Astrocytoma Ivan Urits, Purna Mukherjee, Joshua Meidenbauer, and Thomas N. Seyfried Biology Department, Boston College, Chestnut Hill, MA 0246, USA Correspondence should be addressed to Thomas N. Seyfried, seyfridt@ Received 19 May 2011; Revised 22 September 2011; Accepted 25 September 2011 Academic Editor: Kalpna Gupta Copyright © 2012 Ivan Urits et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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