title: Apelin expression in human non-small cell lung cancer: role in angiogenesis and prognosis.
abstract: BACKGROUND
  The recently discovered bioactive peptide, apelin, has been demonstrated to stimulate angiogenesis in various experimental systems. However, its clinical significance and role in tumor vascularization have not yet been investigated in a human malignancy. Therefore, our aim was to study whether apelin expression is associated with angiogenesis and/or tumor growth/behavior in human non-small cell lung cancer (NSCLC).
  
  
  METHODS
  A total of 94 patients with stage I-IIIA NSCLC and complete follow-up information were included. Apelin expression in human NSCLC samples and cell lines was measured by quantitative reverse-transcriptase polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. Effects of exogenous apelin and apelin transfection were studied on NSCLC cell lines in vitro. In vivo growth of tumors expressing apelin or control vectors were also assessed. Morphometric variables of human and mouse tumor capillaries were determined by anti-CD31 labeling.
  
  
  RESULTS
  Apelin was expressed in all of the six investigated NSCLC cell lines both at the mRNA and protein levels. Although apelin overexpression or apelin treatments did not increase NSCLC cell proliferation in vitro, increasing apelin levels by gene transfer to NSCLC cells significantly stimulated tumor growth and microvessel densities and perimeters in vivo. Apelin mRNA levels were significantly increased in human NSCLC samples compared with normal lung tissue, and high apelin protein levels were associated with elevated microvessel densities and poor overall survival.
  
  
  CONCLUSIONS
  This study reveals apelin as a novel angiogenic factor in human NSCLC. Moreover, it also provides the first evidence for a direct association of apelin expression with clinical outcome in a human cancer.
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Judit
authors.initials: J
authors.lastname: Berta
authors.forename: Istvan
authors.initials: I
authors.lastname: Kenessey
authors.forename: Judit
authors.initials: J
authors.lastname: Dobos
authors.forename: Jozsef
authors.initials: J
authors.lastname: Tovari
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Hendrik
authors.initials: H
authors.lastname: Jan Ankersmit
authors.forename: Balazs
authors.initials: B
authors.lastname: Hegedus
authors.forename: Ferenc
authors.initials: F
authors.lastname: Renyi-Vamos
authors.forename: Janos
authors.initials: J
authors.lastname: Varga
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Lorincz
authors.forename: Sandor
authors.initials: S
authors.lastname: Paku
authors.forename: Gyula
authors.initials: G
authors.lastname: Ostoros
authors.forename: Anita
authors.initials: A
authors.lastname: Rozsas
authors.forename: Jozsef
authors.initials: J
authors.lastname: Timar
authors.forename: Balazs
authors.initials: B
authors.lastname: Dome
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000073861:Apelin; D015153:Blotting, Western; D018287:Carcinoma, Large Cell / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
chemical_list: C115436:APLN protein, human; D000073861:Apelin; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger