Elsevier

Experimental Gerontology

Volume 27, Issues 5–6, September–December 1992, Pages 523-532
Experimental Gerontology

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

https://doi.org/10.1016/0531-5565(92)90007-MGet rights and content

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.

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    Citation Excerpt :

    The present study showed an attenuation of contact inhibition in cell proliferation by TNIIIA2 in both a PDGF- and integrin α5β1-dependent manner. Of note, previous studies demonstrated that, on forced expression of PDGF, NIH3T3 cells undergo a loss of contact-inhibited growth and acquire the ability to grow in soft agar and form tumors in nude mice as a result of autocrine signaling (52, 53). Because coordinated input from RTKs and integrins is necessary for cell cycle progression and proliferation and because both types of receptors activate common members of the Ras/MAP kinase signaling pathway, it is not surprising that sustained activation of integrin α5β1 by TNIIIA2, in the presence of added PDGF, leads to the same result as that induced by stable expression of PDGF.

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