Dose-dependent effects of platelet-derived growth factor-B on glial tumorigenesis

Alan H. Shih, Chengkai Dai, Xiaoyi Hu, Marc K. Rosenblum, Jason A. Koutcher, Eric C. Holland

Research output: Contribution to journalArticlepeer-review

190 Scopus citations

Abstract

Platelet-derived growth factor (PDGF) is expressed in many different tumors, but its precise roles in tumorigenesis remain to be fully defined. Here, we report on a mouse model that demonstrates dose-dependent effects of PDGF-B on glial tumorigenesis. By removing inhibitory regulatory elements in the PDGFB mRNA, we are able to substantially elevate its expression in tumor cells using a retroviral delivery system. This elevation in PDGF-B production results in tumors with shortened latency, increased cellularity, regions of necrosis, and general high-grade character. In addition, elevated PDGF-B in these tumors also mediates vascular smooth muscle cell recruitment that supports tumor angiogenesis. PDGF receptor (PDGFR) signaling appears to be required for the maintenance of these high-grade characteristics, because treatment of high-grade tumors with a small molecule inhibitor of PDGFR results in reversion to a lower grade tumor histology. Our data show that PDGFR signaling quantitatively regulates tumor grade and is required to sustain high-grade oligodendrogliomas.

Original languageEnglish
Pages (from-to)4783-4789
Number of pages7
JournalCancer Research
Volume64
Issue number14
DOIs
StatePublished - 15 Jul 2004
Externally publishedYes

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