The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma

Jun Muto, Ken Shirabe, Tomoharu Yoshizumi, Toru Ikegami, Shinichi Aishima, Kosei Ishigami, Yoshikazu Yonemitsu, Tetsuo Ikeda, Yuji Soejima, Yoshihiko Maehara

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Abstract

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.

Original languageEnglish
Pages (from-to)5313-5320
Number of pages8
JournalAnticancer research
Volume34
Issue number10
Publication statusPublished - Oct 1 2014

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Hepatocellular Carcinoma
Arterioles
Neoplasms
Blood Vessels
Angiogenesis Inducing Agents
Growth and Development
Smooth Muscle
Arteries
Growth
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Muto, J., Shirabe, K., Yoshizumi, T., Ikegami, T., Aishima, S., Ishigami, K., ... Maehara, Y. (2014). The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma. Anticancer research, 34(10), 5313-5320.

The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma. / Muto, Jun; Shirabe, Ken; Yoshizumi, Tomoharu; Ikegami, Toru; Aishima, Shinichi; Ishigami, Kosei; Yonemitsu, Yoshikazu; Ikeda, Tetsuo; Soejima, Yuji; Maehara, Yoshihiko.

In: Anticancer research, Vol. 34, No. 10, 01.10.2014, p. 5313-5320.

Research output: Contribution to journalArticle

Muto, J, Shirabe, K, Yoshizumi, T, Ikegami, T, Aishima, S, Ishigami, K, Yonemitsu, Y, Ikeda, T, Soejima, Y & Maehara, Y 2014, 'The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma', Anticancer research, vol. 34, no. 10, pp. 5313-5320.
Muto, Jun ; Shirabe, Ken ; Yoshizumi, Tomoharu ; Ikegami, Toru ; Aishima, Shinichi ; Ishigami, Kosei ; Yonemitsu, Yoshikazu ; Ikeda, Tetsuo ; Soejima, Yuji ; Maehara, Yoshihiko. / The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma. In: Anticancer research. 2014 ; Vol. 34, No. 10. pp. 5313-5320.
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