Expression of Heparin-binding Epidermal Growth Factor in Human Hepatocellular Carcinoma

Background/aims: Growth factors are involved in the development and progression of cancer. The purpose of this study was to evaluate the possible role of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which is a member of the EGF family, in the neoplastic transformation of hepatocytes.

Methods: Gene expression and protein production of HB-EGF were investigated in samples of human hepatocellular carcinoma (HCC) from 17 patients using Northern hybridization and immunohistochemical methods.

Results: The amount of HB-EGF messenger RNA was increased in the patients' HCC specimens compared with the surrounding liver tissues. In noncancerous hepatic tissues, HB-EGF was faintly positive in hepatocytes. Immunoreactive HB-EGF-producing cells were identified in HCC cells of all 17 patients with HCC, indicating that HB-EGF was produced in HCC cells themselves. However, none of the specimens from 10 patients with metastatic adenocarcinoma in the liver was positive for HB-EGF. The EGF receptor, which binds to HB-EGF, was also expressed on HCC cells.

Conclusions: It is hypothesized that the enhanced expression of immunoreactive HB-EGF on the cell suggests a possible role of HB-EGF in the development or progression of human HCC in an autocrine and/or a juxtacrine manners.