The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma

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

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


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
Issue number10
Publication statusPublished - Oct 1 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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