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

Judit Berta, I. Kenessey, J. Dobos, J. Tóvári, Walter Klepetko, Hendrik Jan Ankersmit, B. Hegedűs, Ferenc Renyi-Vamos, Janos Varga, Zsolt Lorincz, S. Paku, G. Ostoros, Anita Rozsas, J. Tímár, B. Döme

Research output: Contribution to journalArticle

57 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

Fingerprint

Non-Small Cell Lung Carcinoma
Neoplasms
Microvessels
Cell Line
Growth
Messenger RNA
Angiogenesis Inducing Agents
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Proteins
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Cell Proliferation
Lung
Peptides
Survival
Genes

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Apelin expression in human non-small cell lung cancer : Role in angiogenesis and prognosis. / Berta, Judit; Kenessey, I.; Dobos, J.; Tóvári, J.; Klepetko, Walter; Jan Ankersmit, Hendrik; Hegedűs, B.; Renyi-Vamos, Ferenc; Varga, Janos; Lorincz, Zsolt; Paku, S.; Ostoros, G.; Rozsas, Anita; Tímár, J.; Döme, B.

In: Journal of Thoracic Oncology, Vol. 5, No. 8, 08.2010, p. 1120-1129.

Research output: Contribution to journalArticle

Berta, Judit ; Kenessey, I. ; Dobos, J. ; Tóvári, J. ; Klepetko, Walter ; Jan Ankersmit, Hendrik ; Hegedűs, B. ; Renyi-Vamos, Ferenc ; Varga, Janos ; Lorincz, Zsolt ; Paku, S. ; Ostoros, G. ; Rozsas, Anita ; Tímár, J. ; Döme, B. / Apelin expression in human non-small cell lung cancer : Role in angiogenesis and prognosis. In: Journal of Thoracic Oncology. 2010 ; Vol. 5, No. 8. pp. 1120-1129.
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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.",
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T1 - Apelin expression in human non-small cell lung cancer

T2 - Role in angiogenesis and prognosis

AU - Berta, Judit

AU - Kenessey, I.

AU - Dobos, J.

AU - Tóvári, J.

AU - Klepetko, Walter

AU - Jan Ankersmit, Hendrik

AU - Hegedűs, B.

AU - Renyi-Vamos, Ferenc

AU - Varga, Janos

AU - Lorincz, Zsolt

AU - Paku, S.

AU - Ostoros, G.

AU - Rozsas, Anita

AU - Tímár, J.

AU - Döme, B.

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N2 - 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.

AB - 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.

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KW - Non-small cell lung cancer

KW - Prognosis

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