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

  


Authors: Shih, A. H.; Dai, C.; Hu, X.; Rosenblum, M. K.; Koutcher, J. A.; Holland, E. C.
Article Title: Dose-dependent effects of platelet-derived growth factor-B on glial tumorigenesis
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.
Keywords: signal transduction; platelet derived growth factor; controlled study; dose response; nonhuman; receptors, vascular endothelial growth factor; glioma; brain neoplasms; cancer grading; mouse; animals; mice; animal tissue; cell division; gene expression; animal experiment; animal model; transfection; platelet derived growth factor receptor; angiogenesis; neovascularization, pathologic; carcinogenesis; viral gene delivery system; mice, transgenic; regulatory mechanism; messenger rna; platelet-derived growth factor; tumor cell; proto-oncogene proteins c-sis; oligodendroglioma; nih 3t3 cells; retrovirus; receptors, platelet-derived growth factor; 5' untranslated regions; glia; platelet derived growth factor b; tumor necrosis; vascular smooth muscle; priority journal; article
Journal Title: Cancer Research
Volume: 64
Issue: 14
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2004-07-15
Start Page: 4783
End Page: 4789
Language: English
DOI: 10.1158/0008-5472.can-03-3831
PROVIDER: scopus
PUBMED: 15256447
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-3142713010&partnerID=40&md5=bb5f73b1850492c684bdbf04da4dccc6
Notes: Cancer Res. -- Cited By (since 1996):132 -- Export Date: 16 June 2014 -- CODEN: CNREA -- Source: Scopus
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MSK Authors
  1. Marc Rosenblum
    424 Rosenblum
  2. Eric Holland
    225 Holland
  3. Alan H Shih
    59 Shih
  4. Jason A Koutcher
    278 Koutcher
  5. Xiaoyi Hu
    8 Hu
  6. Chengkai Dai
    9 Dai
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