Elliott Steve, Sinclair Angus M
Oncology Research, Amgen, Thousand Oaks, CA, USA.
Biologics. 2012;6:163-89. doi: 10.2147/BTT.S32281. Epub 2012 Jun 27.
Erythropoietin (Epo) is an essential hormone that binds and activates the Epo receptor (EpoR) resident on the surface of erythroid progenitor cells, thereby promoting erythropoiesis. Recombinant human erythropoietin has been used successfully for over 20 years to treat anemia in millions of patients. In addition to erythropoiesis, Epo has also been reported to have other effects, such as tissue protection and promotion of tumor cell growth or survival. This became of significant concern in 2003, when some clinical trials in cancer patients reported increased tumor progression and worse survival outcomes in patients treated with erythropoiesis-stimulating agents (ESAs). One of the potential mechanisms proffered to explain the observed safety issues was that functional EpoR was expressed in tumors and/or endothelial cells, and that ESAs directly stimulated tumor growth and/or antagonized tumor ablative therapies. Since then, numerous groups have performed further research evaluating this potential mechanism with conflicting data and conclusions. Here, we review the biology of endogenous Epo and EpoR expression and function in erythropoiesis, and evaluate the evidence pertaining to the expression of EpoR on normal nonhematopoietic and tumor cells.
促红细胞生成素（Epo）是一种重要的激素，它能与红系祖细胞表面的促红细胞生成素受体（EpoR）结合并激活该受体，从而促进红细胞生成。重组人促红细胞生成素已成功应用20多年，用于治疗数百万患者的贫血。除了红细胞生成作用外，据报道Epo还有其他作用，如组织保护以及促进肿瘤细胞生长或存活。2003年，这一情况引起了人们的极大关注，当时一些针对癌症患者的临床试验报告称，接受促红细胞生成素刺激剂（ESAs）治疗的患者肿瘤进展加快，生存结果更差。为解释所观察到的安全问题而提出的一种潜在机制是，功能性EpoR在肿瘤和/或内皮细胞中表达，并且ESAs直接刺激肿瘤生长和/或拮抗肿瘤消融治疗。从那时起，许多研究小组进行了进一步研究，以评估这一潜在机制，得出的数据和结论相互矛盾。在此，我们综述内源性Epo的生物学特性以及EpoR在红细胞生成中的表达和功能，并评估有关EpoR在正常非造血细胞和肿瘤细胞上表达的证据。
