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

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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