Erythropoietin Receptor Expression Is a Potential Prognostic Factor in Human Lung Adenocarcinoma
(2013) In PLoS ONE 8(10).- 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... (More)
- 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 rHuEPO alpha were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPO alpha 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, rHuEPO alpha treatment (either alone or in combination with gemcitabine) did not alter ADC cell proliferation in vitro. However, rHuEPO alpha significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPO alpha 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4212842
- author
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 8
- issue
- 10
- article number
- e77459
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000325887300092
- scopus:84885400062
- pmid:24155958
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0077459
- language
- English
- LU publication?
- yes
- id
- 1225c846-23f0-4717-88c2-def3eb2b02a1 (old id 4212842)
- date added to LUP
- 2016-04-01 13:17:33
- date last changed
- 2022-02-26 20:24:02
@article{1225c846-23f0-4717-88c2-def3eb2b02a1,
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 rHuEPO alpha were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPO alpha 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, rHuEPO alpha treatment (either alone or in combination with gemcitabine) did not alter ADC cell proliferation in vitro. However, rHuEPO alpha significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPO alpha 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.}},
author = {{Rozsas, Anita and Berta, Judit and Rojko, Livia and Horvath, Laszlo Z. and Keszthelyi, Magdolna and Kenessey, Istvan and Laszlo, Viktoria and Berger, Walter and Grusch, Michael and Hoda, Mir Alireza and Török, Silvia and Klepetko, Walter and Renyi-Vamos, Ferenc and Hegedus, Balazs and Doeme, Balazs and Tovari, Jozsef}},
issn = {{1932-6203}},
language = {{eng}},
number = {{10}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Erythropoietin Receptor Expression Is a Potential Prognostic Factor in Human Lung Adenocarcinoma}},
url = {{http://dx.doi.org/10.1371/journal.pone.0077459}},
doi = {{10.1371/journal.pone.0077459}},
volume = {{8}},
year = {{2013}},
}