Platelet-derived growth factor-B enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment

Ping Guo, Bo Hu, Weisong Gu, Li Xu, Degui Wang, Hui Jen Su Huang, Webster K. Cavenee, Shi Yuan Cheng*

*Corresponding author for this work

Research output: Contribution to journalArticle

247 Scopus citations

Abstract

Platelet-derived growth factor (PDGF)-B and its receptor (PDGF-R) β are overexpressed in human gliomas and responsible for recruiting peri-endothelial cells to vessels. To establish the role of PDGF-B in glioma angiogenesis, we overexpressed PDGF-B in U87MG glioma cells. Although PDGF-B stimulated tyrosine phosphorylation of PDGF-Rβ in U87MG cells, treatment with recombinant PDGF-B or overexpression of PDGF-B in U87MG cells had no effect on their proliferation. However, an increase of secreted PDGF-B in conditioned media of U87MG/PDGF-B cells promoted migration of endothelial cells expressing PDGF-Rβ, whereas conditioned media from U87MG cells did not increase the cell migration. In mice, overexpression of PDGF-B in U87MG cells enhanced intracranial glioma formation by stimulating vascular endothelial growth factor (VEGF) expression in neovessels and by attracting vessel-associated pericytes. When PDGF-B and VEGF were overexpressed simultaneously by U87MG tumors, there was a marked increase of capillary-associated pericytes as seen in U87MG/VEGF 165 /PDGF-B gliomas. As a result of pericyte recruitment, vessels induced by VEGF in tumor vicinity migrated into the central regions of these tumors. These data suggest that PDGF-B is a paracrine factor in U87MG gliomas, and that PDGF-B enhances glioma angiogenesis, at least in part, by stimulating VEGF expression in tumor endothelia and by recruiting pericytes to neovessels.

Original languageEnglish (US)
Pages (from-to)1083-1093
Number of pages11
JournalAmerican Journal of Pathology
Volume162
Issue number4
DOIs
StatePublished - Apr 1 2003

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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