| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
1 Departments of Cancer Biology and Genetics; 2 Pathology; 3 Medicine, Radiology, and Medical Physics; and 4 Surgery (Neurosurgery) and Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York
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.
This article has been cited by other articles:
|
|
 |
|
  C. Beadle, M. C. Assanah, P. Monzo, R. Vallee, S. S. Rosenfeld, and P. Canoll The Role of Myosin II in Glioma Invasion of the Brain Mol. Biol. Cell, August 1, 2008; 19(8): 3357 - 3368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. J. Becher, D. Hambardzumyan, E. I. Fomchenko, H. Momota, L. Mainwaring, A.-M. Bleau, A. M. Katz, M. Edgar, A. M. Kenney, C. Cordon-Cardo, et al. Gli Activity Correlates with Tumor Grade in Platelet-Derived Growth Factor-Induced Gliomas Cancer Res., April 1, 2008; 68(7): 2241 - 2249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Hoelzinger, T. Demuth, and M. E. Berens Autocrine Factors That Sustain Glioma Invasion and Paracrine Biology in the Brain Microenvironment J Natl Cancer Inst, November 7, 2007; 99(21): 1583 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. B. Furnari, T. Fenton, R. M. Bachoo, A. Mukasa, J. M. Stommel, A. Stegh, W. C. Hahn, K. L. Ligon, D. N. Louis, C. Brennan, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment Genes & Dev., November 1, 2007; 21(21): 2683 - 2710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. McConville, D. Hambardzumyan, J. B. Moody, W. R. Leopold, A. R. Kreger, M. J. Woolliscroft, A. Rehemtulla, B. D. Ross, and E. C. Holland Magnetic Resonance Imaging Determination of Tumor Grade and Early Response to Temozolomide in a Genetically Engineered Mouse Model of Glioma Clin. Cancer Res., May 15, 2007; 13(10): 2897 - 2904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Fomchenko and E. C. Holland Mouse models of brain tumors and their applications in preclinical trials. Clin. Cancer Res., September 15, 2006; 12(18): 5288 - 5297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Assanah, R. Lochhead, A. Ogden, J. Bruce, J. Goldman, and P. Canoll Glial progenitors in adult white matter are driven to form malignant gliomas by platelet-derived growth factor-expressing retroviruses. J. Neurosci., June 21, 2006; 26(25): 6781 - 6790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Dresemann Imatinib and hydroxyurea in pretreated progressive glioblastoma multiforme: a patient series Ann. Onc., October 1, 2005; 16(10): 1702 - 1708. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
