Miyamoto Shingo, Yagi Hiroshi, Yotsumoto Fusanori, Horiuchi Shinji, Yoshizato Toshiyuki, Kawarabayashi Tatsuhiko, Kuroki Masahide, Mekada Eisuke
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, 45-1, 7-chome Nanakuma, Jonan-ku, Fukuoka, Japan.
Anticancer Res. 2007 Nov-Dec;27(6A):3713-21.
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.
肝素结合表皮生长因子样生长因子（HB-EGF）是表皮生长因子受体配体之一，具有多个功能域。它通过与各种分子相互作用，参与多种生物学过程，包括伤口愈合、胚泡着床、动脉粥样硬化和肿瘤形成。我们曾报道，HB-EGF基因表达在人类卵巢癌中显著升高，并进一步证明HB-EGF在卵巢癌恶性表型的获得中发挥关键作用，如在腹水中的细胞存活、在细胞外基质上的细胞黏附、侵袭、血管生成、致瘤性和化疗耐药性。因此，HB-EGF被认为是癌症治疗的一个有前景的靶点。体外和体内实验均表明，HB-EGF的特异性抑制剂交叉反应物质197（CRM197）或针对HB-EGF的小干扰RNA可阻断腹膜播散所涉及的各个步骤。基于这些证据，开发针对HB-EGF的靶向工具，如CRM197，可能会改善癌症患者的预后。
