Suramin, an experimental chemotherapeutic drug, activates the receptor for epidermal growth factor and promotes growth of certain malignant cells.
Previous studies have shown that suramin is capable of disrupting autocrine growth involving coexpression of platelet-derived growth factor and its receptors in a fibroblast model for mesenchymal oncogenesis. Suramin is currently in use as an experimental drug for the treatment of patients with epithelial cell tumors. In the present study, we have investigated the efficacy of suramin in a carcinoma model system. Our findings demonstrate that suramin enhances cell surface signaling in A431 cells by activating an autocrine loop involving the receptor for epidermal growth factor (EGFR). The mechanism of suramin action was shown to be indirect, not affecting the ability of ligand to bind and activate the EGFR. Instead, suramin induced the release of membrane-bound transforming growth factor alpha, thereby increasing its potential to activate cell surface EGFRs. Since suramin potently blocks tyrosine phosphorylation induced by platelet-derived growth factor but can activate the growth pathway regulated by the EGFR, biological responses of tumor cells to suramin treatment may differ dramatically.
Cardinali
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Laboratory of Cellular Development and Oncology, National Institute of Dental Research, Bethesda, Maryland 20892.
Sartor
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O
Robbins
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KC
D002455:Cell Division / Q000187:drug effects; D066246:ErbB Receptors / Q000032:analysis / Q000187:drug effects*; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D010766:Phosphorylation; D013498:Suramin / Q000494:pharmacology*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism
D016211:Transforming Growth Factor alpha; D014443:Tyrosine; D013498:Suramin; D066246:ErbB Receptors