title: Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma.
abstract: Recombinant human erythropoietins (rHuEPOs) are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR) signaling in human non-small cell lung cancer (NSCLC) also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC) and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOα were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOα with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC) proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU) incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOα treatment (either alone or in combination with gemcitabine) did not alter ADC cell proliferation in vitro. However, rHuEPOα significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOα treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.
authors.affiliation: Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary ; Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Anita
authors.initials: A
authors.lastname: Rózsás
authors.forename: Judit
authors.initials: J
authors.lastname: Berta
authors.forename: Lívia
authors.initials: L
authors.lastname: Rojkó
authors.forename: László Z
authors.initials: LZ
authors.lastname: Horváth
authors.forename: Magdolna
authors.initials: M
authors.lastname: Keszthelyi
authors.forename: István
authors.initials: I
authors.lastname: Kenessey
authors.forename: Viktória
authors.initials: V
authors.lastname: László
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.forename: Michael
authors.initials: M
authors.lastname: Grusch
authors.forename: Mir Alireza
authors.initials: MA
authors.lastname: Hoda
authors.forename: Szilvia
authors.initials: S
authors.lastname: Török
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Ferenc
authors.initials: F
authors.lastname: Rényi-Vámos
authors.forename: Balázs
authors.initials: B
authors.lastname: Hegedűs
authors.forename: Balázs
authors.initials: B
authors.lastname: Döme
authors.forename: József
authors.initials: J
authors.lastname: Tóvári
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001999:Bronchoscopy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D017467:Receptors, Erythropoietin / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D003841:Deoxycytidine; D000093542:Gemcitabine