Apelin expression in human non-small cell lung cancer: Role in angiogenesis and prognosis

Judit Berta, Istvan Kenessey, Judit Dobos, Jozsef Tovari, Walter Klepetko, Hendrik Jan Ankersmit, Balazs Hegedus, Ferenc Renyi-Vamos, Janos Varga, Zsolt Lorincz, Sandor Paku, Gyula Ostoros, Anita Rozsas, Jozsef Timar, Balazs Dome

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Introdution: 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.

Original languageEnglish
Pages (from-to)1120-1129
Number of pages10
JournalJournal of Thoracic Oncology
Volume5
Issue number8
DOIs
Publication statusPublished - Aug 2010

Keywords

  • Angiogenesis
  • Apelin
  • Non-small cell lung cancer
  • Prognosis

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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