Tóvári József, Pirker Robert, Tímár József, Ostoros Gyula, Kovács Gábor, Döme Balázs
Department of Tumor Biology, National Koranyi Institute of Pulmonology, Piheno u 1, Budapest, H-1529, Hungary.
Curr Mol Med. 2008 Sep;8(6):481-91. doi: 10.2174/156652408785747979.
Erythropoietin (EPO) has long been recognized as the major hematopoietic cytokine regulating normal erythropoiesis. Moreover, there is a growing interest in the non-erythropoietic, tissue-protective effects of EPO. Because of its potential to correct anemia, EPO has been increasingly prescribed to cancer patients. However, although recombinant human Epo (rHuEPO) significantly reduces the risk for red blood cell transfusions in cancer patients, recent clinical studies have reported decreased survival and disease control following rHuEPO treatment in patients with different cancer types. The issue of EPOR expression in tumor cells is critical in this respect. The expression of EPOR in tumor cells raises the possibility that exogenous rHuEPO may directly influence tumor growth or sensitivity to chemo-radiation therapy. In addition, EPOR expression in endothelial cells suggests what potential effects EPO may have on tumor capillaries, such as the stimulation of angiogenesis. However, as experimental studies reveal, the overall direct effect of EPO-EPOR signaling on cancer progression and therapy is not a straightforward one. The current paper provides an update on the biology of EPO, and discusses its utility in the treatment of cancer patients.
促红细胞生成素(EPO)长期以来一直被认为是调节正常红细胞生成的主要造血细胞因子。此外,人们对EPO的非促红细胞生成的组织保护作用的兴趣与日俱增。由于EPO具有纠正贫血的潜力,它越来越多地被开给癌症患者。然而,尽管重组人促红细胞生成素(rHuEPO)显著降低了癌症患者红细胞输血的风险,但最近的临床研究报告称,在不同癌症类型的患者中,rHuEPO治疗后生存率和疾病控制率有所下降。在这方面,肿瘤细胞中促红细胞生成素受体(EPOR)的表达问题至关重要。肿瘤细胞中EPOR的表达增加了外源性rHuEPO可能直接影响肿瘤生长或对放化疗敏感性的可能性。此外,内皮细胞中EPOR的表达表明EPO可能对肿瘤毛细血管有潜在影响,如刺激血管生成。然而,正如实验研究所揭示的,EPO-EPOR信号对癌症进展和治疗的总体直接影响并非简单直接。本文提供了关于EPO生物学的最新信息,并讨论了其在癌症患者治疗中的效用。