SUTUDIES ON THE RELATIONSHIP BETWEEN EPIDERMAL GROWTH FACTOR FAMILY EXPRESSION AND CARCINIGENESIS AND PROGESSION OF HEPATODELLULAR CRACINOMA : A SPECIAL REFERENCE TO HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH FACTOR EXPRESSION

应用免疫组化技术比较研究HB-EGF在人肝细胞癌（HCC）和非HCC组织中的表达。肝细胞和HCC细胞细胞质中均表达肝素结合生长因子样生长因子（HB-EGF）。由于HB-EGF的阳性率和染色强度在肝细胞瘤化转化后呈增加趋势，且染色强度随HCC的组织学分级呈增加趋势，提示HB-EGF可能在HCC的发生发展中起作用。肉瘤性HCC的免疫染色倾向于在肉瘤成分中比在HCC成分中表现出更强的强度。在癌变和非癌变鼻窦的巨噬细胞、成纤维细胞和内皮细胞中也发现HB-EGF的表达。这些结果提示HCC细胞可能具有由HB-EGF和表皮生长因子（EGF）受体介导的自分泌和旁分泌机制调节的增殖机制。HCC细胞系实验显示，HCC细胞频繁表达转化生长因子(TGF)-α，但很少表达HB-EGF。HCC细胞可能具有旁分泌系统，不仅受HB-EGF的调节，还受TGF-α、EGF和双调节蛋白的调节；一种是由未知的EGF家族成员和EGFR调控的自分泌生长机制，一种在一定条件下由TGF-α和EGFR调控。CD9的表达增强了由HB-EGF和EGF受体调控的近肽生长机制，在HCC和非HCC组织的肝细胞和窦壁细胞中均有表达。CD9在高分化HCC组织中的表达高于中分化HCC组织。综上所述，HB-EGF的表达可能与肝癌的发生和HCC的进展有关，高分化HCC的增殖可能不仅受到HB-EGF介导的旁分泌和/或自分泌机制的调节，还可能受到HB=EGF与CD9协同介导的近分泌机制的调节。少

HB-EGF expression was comparatively investigated in human hepatocellular carcinoma (HCC) and non-HCC tissues by using immunohistochemical technique. Both of hepatocytes and HCC cells expressed heparin binding -growth factor-like growth factor (HB-EGF) in the cytoplasm. Since HB-EGF positive rate and staining intensity tended to increase after neoplastic transformation of hepatocytes, and since the staining intensity tended to increase along with the histologic grade of HCC, a possible role of HB-EGF in the development and progression of HCC would be suggested. Sarcomatous HCCs tended to show more intensive immunostaining in the sarcomatous components than in the HCC components. HB-EGF expression was also noted in macrophages, fibroblasts, and endothelial cells in the cancerous and noncancerous sinusoids. These results suggest that HCC dells may possess a proliferation mechanism regulated by an autocrine and a paracrine mechanisms which are mediated by HB-EGF and epidermal growth factor … More (EGF) receptor. HCC cell line experiments revealed that HCC cells frequently express transforming growth factor (TGF)-α, but rarely express HB-EGF. HCC cells may possess a paracrine system regulated not only by HB-EGF, but also by TGF-α, EGF, and amphiregulin ; and an autocrine growth mechanism regulated by an unknown EGF family member and EGFR, one regulated by TGF-α and EGFR under a certain condition. Expression of CD9, which enhances a juxtacrine growth mechanism regulated by HB-EGF and EGF receptor, was observed in hepatocytes, and sinusoidal lining cells in HCC and nonHCC tissues. CD9 expression was more frequently observed in well-differentiated HCC tissues than in moderately differentiated HCC tissues. In conclusion, it was suggested that HB-EGF expression may relate with hepatocarcinogenesis and HCC progression, and that the proliferation of well differentiated HCCs may be regulated not only by a paracrine and/or an autocrine mechanisms mediated by HB-EGF, but also by a juxtacrine mechanism mediated by HB=EGF in cooperation with CD9. Less