A glioma-derived analog to platelet-derived growth factor: demonstration of receptor competing activity and immunological crossreactivity.

Abstract

A human clonal glioma cell line, U-343 MGa Cl 2, cultured under serum-free conditions, released a factor that competed with 125I-labeled platelet-derived growth factor (125I-PDGF) for binding to human foreskin fibroblasts. The concentration of competing activity in conditioned medium was equal to 20-30 ng of PDGF/ml. The PDGF receptor competing activity had an elution position on Sephadex G-200 close to that of tracer PDGF. The same fractions in the chromatogram also contained growth-promoting activity and material active in a PDGF radioimmunoassay. Incubation of partially purified, 125I-labeled glioma factor with fibroblasts, or a rabbit anti-PDGF serum, led to the selective binding of a component with an estimated MW of 31,000 as shown by NaDodSO4/gel electrophoresis under nonreducing conditions. After reduction this component migrated as a MW 18,000 protein. The behavior in NaDodSO4/gel electrophoresis was similar to that of PGDF. Incubation of partially purified glioma factor with immobilized PDGF antibodies markedly decreased the amount of PDGF receptor competing activity remaining in the supernatant. The factor produced by glioma cells has structural, immunological and functional resemblance to PDGF. Previously, a human osteosarcoma cell line produced a PDGF-like molecule with growth-promoting activity. Since PDGF is homologous to the transforming gene product of simian sarcoma virus, an autocrine activation of the PDGF receptor may be operational in the growth of human tumors of mesenchymal or glial origin.