Activated platelet-derived growth factor autocrine pathway drives the transformed phenotype of a human glioblastoma cell line.
Human glioblastoma cells (A172) were found to concomitantly express PDGF-BB and PDGF beta-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 (U-343MGa 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 transformed phenotype of the tumor cells, a process that can be blocked by extracellular antagonists.
Vassbotn
F S
FS
Department of Biochemistry and Molecular Biology, University of Bergen.
Ostman
A
A
Langeland
N
N
Holmsen
H
H
Westermark
B
B
Heldin
C H
CH
Nistér
M
M
D000911:Antibodies, Monoclonal; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000096:biosynthesis; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D010982:Platelet-Derived Growth Factor; D004247:DNA; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor