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Background: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is synthesized as a membrane-anchored precursor that is proteolytically cleaved to release the soluble mature growth factor, HB-EGF. The former functions as juxtacrine and the latter as paracrine growth factor. Soluble HB-EGF shows several forms in Western blotting with apparent molecular weights 19~27 kDa due to heterogeneous O-glycosylation and N-terminal truncation. HB-EGF activates EGFR and ErbB4 and promotes the development in many tissues. In human ProHB-EGF is the cellular receptor for diphtheria toxin. Non-toxic mutant of diphtheria toxin, CRM197, inhibits HB-EGF function. As HB-EGF level is elevated in most ovarian cancer, CRM197 is being tested as an anticancer drug. The hybridoma clone 4G10 was established and characterized in the laboratory of Prof. E. Mekada of Osaka University, who is a leading scientist in this field.