Heparin-Binding Epidermal Growth Factor-Like Growth Factor as a New Target Molecule for Cancer Therapy

Abstract

HB-EGF, a member of the EGF family of growth factors, exerts itsbiological activity through activation of the EGFR and other ErbBreceptors. HB-EGF participates in diverse biological processes,including heart development and maintenance, skin woundhealing, eyelid formation, blastocyst implantation, progressionof atherosclerosis and tumor formation, through the activationof signaling molecules downstream of ErbB receptors andinteractions with molecules associated with HB-EGF. Recentstudies have indicated that HB-EGF gene expression issignificantly elevated in many human cancers and its expressionlevel in a number of cancer-derived cell lines is much higher thanthose of other EGFR ligands. Several lines of evidence haveindicated that HB-EGF plays a key role in the acquisition ofmalignant phenotypes, such as tumorigenicity, invasion,metastasis and resistance to chemotherapy. Studies