Expression of erythropoietin and erythropoietin receptor in non-small cell lung carcinomas.
ABSTRACT Expression of erythropoietin (Epo) and its receptor (Epo-R) has been shown in various normal and neoplastic nonhematopoietic tissues. This study, in non-small cell lung carcinoma, was designed to investigate the previously unreported expression of Epo and Epo-R as well as hypoxia-inducible factor-1alpha (HIF-1alpha), which is known to control Epo expression.
Samples from lung squamous cell carcinomas (n = 17) and adenocarcinomas (n = 12) were obtained from patients undergoing curative surgery. mRNA transcripts of Epo, Epo-R, soluble Epo-R (sEpo-R), HIF-1alpha, and factor inhibiting HIF-1 (FIH-1) were evaluated by reverse transcription-PCR, whereas localization of Epo, Epo-R, and HIF-1alpha was assessed by immunohistochemistry.
Epo, Epo-R, sEpo-R, HIF-1alpha, and FIH-1 transcripts were detected by reverse transcription-PCR in all samples tested, but with heterogeneous levels of expression for Epo, Epo-R, and sEpo-R. Coordinated levels of mRNA were observed for HIF-1alpha and FIH-1.Epo was detected in carcinomatous cells by immunohistochemistry in 50% of samples and Epo-R was detected in 96% of samples. Co-expression of Epo and Epo-R was observed on contiguous sections from 50% of tumors. HIF-1alpha was immunolocalized in 80% of non-small cell lung carcinomas.
Epo-R was expressed in almost all samples and Epo was expressed in one half of samples on immunohistochemistry and in 100% of samples by mRNA detection, suggesting a potential paracrine and/or autocrine role of endogenous Epo in non-small cell lung carcinoma. The detection of stabilized HIF-1alpha suggests a possible role in Epo expression. Moreover, in the light of these results, the potential interactions between therapeutic recombinant Epo and the putative neoplastic Epo/Epo-R signaling pathways must be considered.
SourceAvailable from: István Kenessey[Show abstract] [Hide abstract]
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.PLoS ONE 01/2013; 8(10):e77459. DOI:10.1371/journal.pone.0077459 · 3.53 Impact Factor
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ABSTRACT: Objective: The aim of this research is to investigate the relationship between anemia and erythropoietin (Epo) and erythropoietin receptor (EpoR) expression. This study also investigated the relationship between Epo and EpoR expression level and the proliferation rate of cancer cells. Methods: 20 samples of breast cancer tissues were divided into two groups; anemic group (from patiens with Hb level < 12) and non-anemic group (from patients with Hb level > 12). All samples were analyzed by using immunofluorescence staining in order to examine Epo and EpoR expression. Proliferation of cancer cells were analyzed by using Hematoxylin-Eosin staining. Results: Anemic breast cancer group represented higher Epo and EpoR expression than the non-anemic group. The results also indicated that in anemic samples expression levels of Epo and EpoR were negatively correlated with the number of cancer cells. In contrast, Epo and EpoR expression levels from non-anemic samples were positively correlated with the number of cancer cells. Conclusion: These results conducted that anemia is a crucial factor of hypoxic condition. Hypoxia led by anemia cause a different control mechanism of Epo and EpoR expression and cancer cell proliferation.07/2013; 3(3):199-204. DOI:10.5455/jeim.010513.or.069
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ABSTRACT: BackgroundExpressing several markers of migrating primordial germ cells (PGCs), the rare population of quiescent, bone marrow (BM)-residing very small embryonic-like stem cells (VSELs) can be specified like PGCs into hematopoietic stem/progenitor cells (HSPCs). These two properties of VSELs support the possibility of a developmental origin of HSPCs from migrating PGCs.MethodsTo address a potential link between VSELs and germ line cells we analyzed by RT-PCR and FACS expression of erythropoietin receptor (EpoR) on murine bone marrow- and human umbilical cord blood-derived VSELs, murine and human teratocarcinoma cell lines and human ovarian cancer cells. A proper gating strategy and immunostaining excluded from FACS analysis potential contamination by erythroblasts. Furthermore, the transwell chemotaxis assays as well as adhesion and signaling studies were performed to demonstrate functionality of erythropoietin - EpoR axes on these cells.ResultsWe report here that murine and human VSELs as well as murine and human teratocarcinoma cell lines and ovarian cancer cell lines share a functional EpoR.ConclusionsOur data provide more evidence of a potential developmental link between germline cells, VSELs, and HSCs and sheds more light on the developmental hierarchy of the stem cell compartment in adult tissues.Journal of Ovarian Research 06/2014; 7:66. DOI:10.1186/1757-2215-7-66 · 2.03 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.