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The apelin-APJ system regulates angiogenesis, and is overexpressed in several types of cancer. The aim of this study was to clarify the role of the apelin-APJ system in the angiogenesis of hepatocellular carcinoma (HCC). Expressions of angiogenic factors and vascular markers were investigated in specimens from 90 HCC patients. A subcutaneous HCC tumor mouse model was treated with the APJ antagonist, F13A, and tumor growth and vascular development were assessed. APJ expression was observed in arteriole-smooth muscle. Higher amounts of APJ(+)-arteriole and apelin were detected in tumors (p<0.001 for both). APJ(+)-arteriole and apelin expression were more commonly observed in moderately- and poorly-differentiated than in well-differentiated HCC (p ≤ 0.003). HCC with irregular dilated arteries expressed higher levels of apelin (p=0.012). Tumor growth was inhibited by treatment with F13A (p<0.001), and arterioles were decreased in the treated group (p=0.047), in vivo. Apelin-APJ is overexpressed, and works as a signal for arteriogenesis in HCC. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.


Jun Muto, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Shinichi Aishima, Kousei Ishigami, Yoshikazu Yonemitsu, Tetsuo Ikeda, Yuji Soejima, Yoshihiko Maehara. The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma. Anticancer research. 2014 Oct;34(10):5313-20

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PMID: 25275024

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