Open AccessHeparin‐binding epidermal growth factor‐like growth factor as a novel targeting molecule for cancer therapy
Author(s) -
Miyamoto Shingo,
Yagi Hiroshi,
Yotsumoto Fusanori,
Kawarabayashi Tatsuhiko,
Mekada Eisuke
Publication year - 2006
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2006.00188.x
Subject(s) - heparin binding egf like growth factor , epidermal growth factor , cancer research , erbb , epidermal growth factor receptor , cancer , growth factor receptor inhibitor , metastasis , growth factor , growth factor receptor , receptor , biology , amphiregulin , microbiology and biotechnology , medicine
HB‐EGF, a member of the EGF family of growth factors, exerts its biological activity through activation of the EGFR and other ErbB receptors. HB‐EGF participates in diverse biological processes, including heart development and maintenance, skin wound healing, eyelid formation, blastocyst implantation, progression of atherosclerosis and tumor formation, through the activation of signaling molecules downstream of ErbB receptors and interactions with molecules associated with HB‐EGF. Recent studies have indicated that HB‐EGF gene expression is significantly elevated in many human cancers and its expression level in a number of cancer‐derived cell lines is much higher than those of other EGFR ligands. Several lines of evidence have indicated that HB‐EGF plays a key role in the acquisition of malignant phenotypes, such as tumorigenicity, invasion, metastasis and resistance to chemotherapy. Studies in vitro and in vivo have indicated that HB‐EGF expression is essential for tumor formation of cancer‐derived cell lines. CRM197, a specific inhibitor of HB‐EGF, and an antibody against HB‐EGF are both able to inhibit tumor growth in nude mice. These results indicate that HB‐EGF is a promising target for cancer therapy, and that the development of targeting tools against HB‐EGF could represent a novel type of therapeutic strategy, as an alternative to targeting ErbB receptors. ( Cancer Sci 2006; 97 : 341–347)