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Human Cancer Biology |
1 Service d'Histologie-Biologie Tumorale and 2 Service d'Anatomie Pathologique, Unité Propre de Recherche de l'Enseignement Supérieur EA 3499, Université Paris 6, Hôpital Tenon, Paris, France and 3 Unité Mixte de Recherche-Centre National de la Recherche Scientifique 6185, Université de Caen, Caen, France
Requests for reprints: Patrice Callard, Service d'Anatomie-Pathologique and Unité Propre de Recherche de l'Enseignement Supé rieur EA 3499, Université Paris 6, Hôpital Tenon, 4 rue de la Chine, 75970 Paris cedex 20, France. Phone: 33-1-56-01-70-13; Fax: 33-1-56-01-78-76; E-mail: patrice.callard{at}tnn.ap-hop-paris.fr.
Purpose: Expression of erythropoietin (Epo) and its receptor (Epo-R) has been shown in various normal and neoplastic nonhematopoietic tissues. This study, in nonsmall cell lung carcinoma, was designed to investigate the previously unreported expression of Epo and Epo-R as well as hypoxia-inducible factor-1
(HIF-1
), which is known to control Epo expression.
Experimental Design: 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-1
, and factor inhibiting HIF-1 (FIH-1) were evaluated by reverse transcription-PCR, whereas localization of Epo, Epo-R, and HIF-1
was assessed by immunohistochemistry.
Results: Epo, Epo-R, sEpo-R, HIF-1
, 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-1
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-1
was immunolocalized in 80% of nonsmall cell lung carcinomas.
Conclusion: 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 nonsmall cell lung carcinoma. The detection of stabilized HIF-1
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.
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