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The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma
Jun Muto1, Ken Shirabe2, Tomoharu Yoshizumi3
1Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Aim:
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).
Materials And Methods:
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.
Results:
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.
Conclusion:
Apelin-APJ is overexpressed, and works as a signal for arteriogenesis in HCC.
