Expression of erythropoietin and erythropoietin receptor in non-small cell lung carcinomas.
Expression of erythropoietin and erythropoietin receptor in non-small cell lung carcinomas.
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发表时间：
2005-02
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通讯作者：
Koami Dagnon;E. Pacary;F. Commo;M. Antoine;M. Bernaudin;J. Bernaudin;P. Callard
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作者：
Koami Dagnon;E. Pacary;F. Commo;M. Antoine;M. Bernaudin;J. Bernaudin;P. Callard
促红细胞生成素（Epo）及其受体（Epo-R）在多种正常和肿瘤性非造血组织中均有表达。这项研究，在非小细胞肺癌，旨在调查以前未报道的表达Epo和Epo-R以及缺氧诱导因子-1 α（HIF-1 α），这是已知的控制Epo的表达。实验设计从接受根治性手术的患者获得肺鳞状细胞癌（n = 17）和腺癌（n = 12）的样品。通过逆转录-PCR评估Epo、Epo-R、可溶性Epo-R（sEpo-R）、HIF-1 α和HIF-1抑制因子（FIH-1）的mRNA转录，而通过免疫组织化学评估Epo、Epo-R和HIF-1 α的定位。结果逆转录-PCR法检测到Epo、Epo-R、sEpo-R、HIF-1 α和FIH-1的转录本，但Epo、Epo-R和sEpo-R的表达水平不一致。HIF-1 α和FIH-1 mRNA水平协调一致。免疫组化检测50%的癌细胞表达Epo，96%的癌细胞表达Epo-R。Epo和Epo-R的共表达在50%的肿瘤的连续切片上观察到。HIF-1 α在80%的非小细胞肺癌中表达。结论Epo-R在几乎所有的非小细胞肺癌组织中均有表达，Epo在免疫组化和mRNA检测中分别有1/2和100%表达，提示内源性Epo在非小细胞肺癌中可能具有旁分泌和/或自分泌作用。稳定的HIF-1 α的检测表明可能在Epo表达中起作用。此外，根据这些结果，治疗性重组Epo和推定的肿瘤性Epo/Epo-R信号通路之间的潜在相互作用必须被考虑。
PURPOSE 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. 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-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. RESULTS 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. 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 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.