New approach to cancer therapy: heparin binding-epidermal growth factor-like growth factor as a novel targeting molecule.
Heparin binding-epidermal growth factor-like growth factor (HB-EGF) is one of the EGF receptor ligands and possesses several functional domains. It is involved in diverse biological processes, including wound healing, blast implantation, atherosclerosis and tumor formation, through its interactions with various molecules. We have reported that HB-EGF gene expression is significantly elevated in human ovarian cancer, and further demonstrated that HB-EGF plays key roles in the acquisition of malignant phenotypes, such as cell survival in peritoneal fluid, cell adhesion on extracellular matrices, invasion, angiogenesis, tumorigenicity, and chemoresistance in ovarian cancer. Thus, HB-EGF was considered as a promising target for cancer therapy. In vitro as well as in vivo experiments have revealed that cross-reacting material 197 (CRMI97), a specific inhibitor of HB-EGF, or a small interfering RNA for HB-EGF can block each step involved in peritoneal dissemination. According to these pieces of evidence, the development of targeting tools against HB-EGF, such as CRM197, could allow us to improve the prognosis of cancer patients.
Miyamoto
Shingo
S
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, 45-1, 7-chome Nanakuma, Jonan-ku, Fukuoka, Japan. smiya@cis.fukuoka-u.ac.jp
Yagi
Hiroshi
H
Yotsumoto
Fusanori
F
Horiuchi
Shinji
S
Yoshizato
Toshiyuki
T
Kawarabayashi
Tatsuhiko
T
Kuroki
Masahide
M
Mekada
Eisuke
E
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000627:therapeutic use; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D005260:Female; D005544:Forecasting; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000556:secondary; D013329:Structure-Activity Relationship; D014162:Transfection
D000970:Antineoplastic Agents; D001426:Bacterial Proteins; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; C028581:CRM197 (non-toxic variant of diphtheria toxin)