Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer
Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer
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DOI：
10.1002/ijc.10198
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发表时间：
2002-04-01
影响因子：
6.4
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
--
作者：
Murayama, Y;Miyagawa, J;Matsuzawa, Y
肝素结合表皮生长因子样生长因子（HB-EGF）是EGF家族的成员。proHB-EGF（HB-EGF的膜锚定形式）的邻分泌活性已被证明在体外与CD 9共表达时显著增强。本研究旨在探讨胃癌组织中proHB-EGF和CD 9是否共表达。本研究检测了人胃癌组织中HB-EGF基因表达和蛋白表达，并检测了EGF受体和CD 9的表达。HB-EGF mRNA在胃癌组织中的表达明显高于正常胃组织，尤其在肠型胃癌组织中。ProHB-EGF免疫反应主要见于胃癌细胞的胞浆和质膜。66例中40例（60.6%）表达proHB-EGF，其表达水平与肿瘤状态（p < 0.01）和组织分化程度（p < 0.001）显著相关。此外，原位杂交检测到proHB-EGF mRNA在肠型高水平。36例患者中有26例（72.2%）CD 9免疫反应性保持不变，CD 9蛋白表达与淋巴结状态呈负相关（p < 0.05）。其表达与组织学分化显著相关（p < 0.01），免疫沉淀法证实，CD 9与proHB-EGF的相关性在肠型中增加。提示proHB-EGF和CD 9的共表达可能以协同作用的方式参与胃癌的发生和/或增殖。(C)2002 Wiley-Liss，Inc.
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. (C) 2002 Wiley-Liss, Inc.