Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer

Autor: Jun-ichiro Miyagawa, Hitoshi Mizuno, Koji Isozaki, Yoko Murayama, Shigeki Higashiyama, Shuji Kanayama, Yoshiji Miyazaki, Tatsuya Kiyohara, Yuji Matsuzawa, Yasuhisa Shinomura, Naoyuki Taniguchi, Shingo Ishiguro, Katsumi Yamamori
Rok vydání: 2002
Předmět:
Zdroj: International Journal of Cancer. 98:505-513
ISSN: 1097-0215
0020-7136
DOI: 10.1002/ijc.10198
Popis: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family. Juxtacrine activity of proHB-EGF (the membrane-anchored form of HB-EGF) has been shown to be significantly potentiated when it is coexpressed with CD9 in vitro. The purpose of our study was to investigate the issue of whether proHB-EGF and CD9 are coexpressed in gastric cancer. HB-EGF gene expression and protein production in human gastric cancers was investigated, and EGF receptor and CD9 expressions were also evaluated. HB-EGF mRNA levels in gastric cancers were elevated, compared with normal gastric tissues, especially in the intestinal type. ProHB-EGF immunoreactivity was detected primarily in the cytoplasm and plasma membrane of gastric cancer cells. Of 66 patients, 40 (60.6%) exhibited proHB-EGF immunoreactivity and the level of its expression was significantly associated with tumor status (p < 0.01) and histological differentiation (p < 0.001). In addition, proHB-EGF mRNA was detected at high levels in the intestinal type by in situ hybridization. CD9 immunoreactivity was found to be preserved in 26 of 36 patients (72.2%) and CD9 protein expression was inversely associated with lymph node status (p < 0.05). A significant correlation between its expression and histological differentiation (p < 0.01) was found, and the association of CD9 with proHB-EGF was increased in the intestinal type, as evidenced by an immunoprecipitation method. These results indicate that the coexpression of proHB-EGF and CD9 may be involved in the tumorigenesis and/or proliferation of gastric cancers in a juxtacrine manner.
Databáze: OpenAIRE