Platelet-derived growth factor (PDGF) receptor activation in cell transformation and human malignancy

Timothy P. Fleming, Toshimitsu Matsui, Stuart A. Aaronson

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

We demonstrate that the v-sis-transformed NIH/3T3 fibroblasts exhibit tyrosine-phosphorylation of both intracellular and cell surface forms of the α and β platelet-derived growth factor (PDGF) receptors (PDGFRs). Cell proliferation was partially inhibited by PDGF-neutralizing antibody, but was completely blocked by the drug suramin. Suramin treatment markedly reduced tyrosine-phosphorylated cell surface PDGFRs, but had no effect on the tyrosine-phosphorylated intracellular receptor species. These findings indicate that v-sis-activated PDGFRs must attain a cell surface localization to functionally couple with the mitogenic-signaling pathway. Additionally, we were able to demonstrate a functional autocrine loop involving PDGF in human tumor cell lines. Exposure to suramin resulted in diminished receptor autophosphorylation and/or upregulation of the PDGFRs. A subset of the tumor cell lines possessing a PDGF autocrine pathway exhibited a significant reduction in proliferation after exposure to suramin. These findings indicate that a PDGF autocrine loop contributes to the uncontrolled proliferative drive in some human malignancies.

Original languageEnglish
Pages (from-to)523-532
Number of pages10
JournalExperimental Gerontology
Volume27
Issue number5-6
DOIs
StatePublished - 1992
Externally publishedYes

Keywords

  • PDGF receptors
  • cancer
  • transformation

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