ACTIVATED PLATELET-DERIVED GROWTH-FACTOR AUTOCRINE PATHWAY DRIVES THETRANSFORMED PHENOTYPE OF A HUMAN GLIOBLASTOMA CELL-LINE

Human glioblastoma cells (A172) were found to concomitantly express PD GF-BB and PDCF beta-receptors. The receptors were constitutively autop hosphorylated in the absence of exogenous ligand, suggesting the prese nce of an autocrine PDGF pathway. Neutralizing PDGF antibodies as well as suramin inhibited the autonomous PDGF receptor tyrosine kinase act ivity and resulted in up-regulation of receptor protein. The interrupt ion of the autocrine loop by the PDGF antibodies reversed the transfor med phenotype of the glioblastoma cell, as determined by (1) diminishe d DNA synthesis, (2) inhibition of tumor colony growth, and (3) revers ion of the transformed morphology of the rumor cells. The PDGF antibod ies showed no effect on the DNA synthesis of another glioblastoma cell s line (U343MCa 31L) or on Ki-ras-transformed fibroblasts. The present study demonstrates an endogenously activated PDGF pathway in a sponta neous human glioblastoma cell line. Furthermore, we provide evidence t hat the autocrine PDGF pathway drives the transformed phenotype of the tumor cells, a process that can be blocked by extracellular antagonis ts.