Activated platelet-derived growth factor autocrine pathway drives the transformed phenotype of a human glioblastoma cell line
Article first published online: 4 FEB 2005
Copyright © 1994 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 158, Issue 2, pages 381–389, February 1994
How to Cite
Vassbotn, F. S., Östman, A., Langeland, N., Holmsen, H., Westermark, B., Heldin, C.-H. and Nistér, M. (1994), Activated platelet-derived growth factor autocrine pathway drives the transformed phenotype of a human glioblastoma cell line. J. Cell. Physiol., 158: 381–389. doi: 10.1002/jcp.1041580221
- Issue published online: 4 FEB 2005
- Article first published online: 4 FEB 2005
- Manuscript Accepted: 10 SEP 1993
- Manuscript Received: 11 JUN 1993
Human glioblastoma cells (A172) were found to concomitantly express PDGF-BB and PDGF β-receptors. The receptors were constitutively autophosphorylated in the absence of exogenous ligand, suggesting the presence of an autocrine PDGF pathway. Neutralizing PDGF antibodies as well as suramin inhibited the autonomous PDGF receptor tyrosine kinase activity and resulted in up-regulation of receptor protein. The interruption of the autocrine loop by the PDGF antibodies reversed the transformed phenotype of the glioblastoma cell, as determined by (1) diminished DNA synthesis, (2) inhibition of tumor colony growth, and (3) reversion of the transformed morphology of the tumor cells. The PDGF antibodies showed no effect on the DNA synthesis of another glioblastoma cells line (U343MGa 31L) or on Ki-ras-transformed fibroblasts. The present study demonstrates an endogenously activated PDGF pathway in a spontaneous human glioblastoma cell line. Furthermore, we provide evidence that the autocrine PDGF pathway drives the transtormed phenotype of the tumor cells, a process that can be blocked by extracellular antagonists. © 1994 Wiley-Liss, Inc.