Expression of Vascular Endothelial Growth Factor in Hepatocellular Carcinoma Cell Lines and Patients

Abstract

Objective: The vascular endothelial growth factor (VEGF) is thought to take an important role in tumor angiogenesis. The present study examined VEGF expression in the liver cancer cell lines and human liver cancer of various differetiated degrees. Methods: Four human hepatocellular carcinoma cell lines with varying degrees of differentiation, namely: Hep 3B (well differentiated), J5 (moderately differentiated), and Mahlavu plus SK-Hep-I (poorly differentiated) were used. For measuring VEGF, culture cells (5-7.5×10^5/ml) were seeded onto 100mm dishes for 24 hours. The amount of secreted VEGF in the culture medium of the cells was measured by the enzymelinked immunosorbent assay (ELISA) method. Forty-three male patients of hepatocellular carcinoma (HCC) were encountered for measuring the serum VEGF level with relationship with cancer cell differentiation. Results: In all four cell lines, VEGF was secreted to the culture supernatants. After 24-hour culture, the VEGF secretion levels were as follows: 332.4±88.1 in Hep 3B; 204.4±49.4 in J5; 111.7±28.4 in Mahlavu; 54.01±6.1 in SK-Hep-I. VEGF secretion in SK-Hep-I was the lowest. In the HCC patients, the serum VEGF level were 423.4±115.5, 356.7±106.5, and 116±45.6 ng/dl for different cancer cell types: well, moderately and poor differentiated groups respectively. In this study, the highest concentration of VEGF was obtained in the well differentiated liver cancer cells. Conclusions: The expression of VEGF was higher in the well or moderately differentiated liver cancer cell in vivo or in vitro study. Clinical biological behavior of poorly differentiated liver cancer may not have resulted from VEGF alone. This study indicats that the high concentration of VEGF has clinical meaning in well differentiated HCC which usually is not presented in the late stage of hepatocarcinogenesis. Therefore, if we try to apply any anti-angiognetic agents to treat HCC, we suggest that the patients are well differentiated HCC.