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Expression of vascular endothelial growth factor in human hepatocellular carcinoma
Author(s) -
Yamaguchi Rin,
Yano Hirohisa,
Iemura Akihiro,
Ogasawara Sachiko,
Haramaki Makoto,
Kojiro Masamichi
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510280111
Subject(s) - hccs , vascular endothelial growth factor , angiogenesis , hepatocellular carcinoma , transforming growth factor , biology , pathology , growth factor , basic fibroblast growth factor , epidermal growth factor , cancer research , cytokine , vascular endothelial growth factor a , cell culture , medicine , endocrinology , immunology , vegf receptors , genetics , receptor
Vascular endothelial growth factor (VEGF) is thought to take an important role in tumor angiogenesis. The present study examined VEGF expression immunohistochemically in hepatocellular carcinomas (HCCs) in various histological grades and sizes. In HCCs that were composed of cancerous tissues of single histological grade, VEGF expression was the highest in well‐differentiated HCCs, followed by moderately differentiated HCCs, and then poorly differentiated HCCs. VEGF positivity gradually decreased with the increase in tumor size. In the nodules larger than 3.0 cm, 36.8% were VEGF‐negative. In HCCs consisting of cancerous tissues of two different histological grades, the expression was less intensive in the higher‐grade HCC component. VEGF was not expressed in sarcomatous areas, while VEGF was expressed in the surrounding HCC tissues. The expression was also remarkable in the noncancerous tissues in which inflammatory cell infiltration was apparent. VEGF expression was also examined in six HCC cell lines. In reverse‐transcription polymerase chain reaction (RT‐PCR) analysis, expressions of the two secretion types (VEGF 121 and VEGF 165 )were the highest. Thus, VEGF protein in culture supernatant was measured by using enzyme‐linked immunosorbent assay (ELISA) with or without inflammatory cytokines, i.e., interleukin (IL)‐1β, interferon (IFN)‐α, IFN‐γ, and tumor necrosis factor (TNF)‐α; and growth factors, i.e., epidermal growth factor (EGF), platelet‐derived growth factor (PDGF)‐BB, basic fibroblast growth factor (bFGF), and transforming growth factor (TGF)‐α. As a result, secretion of VEGF from the cell lines was up‐regulated at various degrees. Based on these findings, VEGF expression in HCC tissues was thought to be related to the histological grade. The findings also indicate that various cytokines and growth factors could cooperatively act to enhance VEGF expressions in HCC.