title: The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  Apelin-APJ is overexpressed, and works as a signal for arteriogenesis in HCC.
authors.affiliation: Department 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Muto
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan kshirabe@surg2.med.kyushu-u.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Yoshizumi
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ikegami
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Aishima
authors.affiliation: Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kousei
authors.initials: K
authors.lastname: Ishigami
authors.affiliation: R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yonemitsu
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Soejima
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000792:Angiography; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C532492:apelin-13, Ala(13)-
keywords: APJ; Apelin; angiogenesis; arteriogenesis; hepatocellular carcinoma