The binding of HB-EGF to tumour cells is blocked by mAbs which act as EGF and TGF alpha antagonists.
Heparin binding EGF (HB-EGF), a newly discovered member of the EGF family of mitogens, binds to the EGF receptor (EGFR) and to heparan sulfate proteoglycans on the cell surface. Here, we show that the binding of HB-EGF to the EGFR is inhibited by mAbs which prevent the interaction of EGF and TGF alpha with the receptor. Also, we show that, like EGF and TGF alpha, treatment with HB-EGF inhibits the growth in vitro of tumours (HN5, HSC-4) that overexpress the EGFR. We conclude that mAbs which act as EGF and TGF alpha antagonists should also be effective therapeutic agents for blocking the growth of EGFR overexpressing tumours induced by HB-EGF.
Institute of Cancer Research, Section of Immunology, Belmont, Sutton, UK.
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D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006258:Head and Neck Neoplasms; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D011485:Protein Binding; D011863:Radioimmunoassay; D016211:Transforming Growth Factor alpha / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D006493:Heparin; D066246:ErbB Receptors