An adiponectin receptor, T-cadherin, was selectively expressed in intratumoral capillary endothelial cells in hepatocellular carcinoma: possible cross talk between T-cadherin and FGF-2 pathways
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T-cadherin is a unique receptor of adiponectin, which plays a critical role in various angiogenesis. In the present study, T-cadherin expression in tumor vessels of hepatocellular carcinoma (HCC) and, subsequently, the molecular mechanism, which induced T-cadherin expression in sinusoidal endothelial cells were investigated. Sinusoidal endothelium in nontumorous liver, chronic hepatitis, or liver cirrhosis expressed little or no T-cadherin. By contrast, T-cadherin was found in intratumoral capillary endothelial cells of 34 out of 63 HCC specimens. In positive cases, focal T-cadherin expression was found in well-differentiated HCC, whereas diffuse and intense T-cadherin expression was observed in poorly differentiated HCC specimens. T-cadherin was much expressed in intratumoral capillary endothelial cells in a less differentiated HCC region than that in a well-differentiated region in five specimens, in which various differentiated HCC components were coexistent. In a double-cell chamber assay, fibroblast growth factor-2 appeared to have a critical role to induce T-cadherin in cultured liver sinusoidal endothelial cells. The present finding indicated that T-cadherin was selectively expressed in intratumoral capillary endothelial cells of many HCCs, increasingly expressed as tumor progression, and T-cadherin may have a positive role in angiogenesis of HCC. In addition, cross talk between the signal pathways mediated by fibroblast growth factor-2 and adiponectin was suggested.
KeywordsT-cadherin Adiponectin Hepatocellular carcinoma Neovascularization
We thank Mr. Yamaguchi, Takuya, Ms. Nakamura, Naoyo (Department of Pathology, Kochi Medical School), and Ms. Matumura, Rumi (Division of Molecular Biology, Kochi Medical School) for skillful technique. This study was supported by grants from the Ministry of Education of Japan (KAKEN 12670165, 13670177, and 17590270) and the Medical Research Fund of Kochi Medical School.
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