促红细胞生成素及其受体在恶性肿瘤组织中的表达及功能的研究进展

促红细胞生成素(erythropoietin,EPO)最早被发现在红系细胞增殖、分化中发挥主要调节作用。研究发现在多种不同非造血器官及组织中有EPO及促红细胞生成素受体(erythropoietin receptor,EPO-R)的表达,并发挥促血管形成及组织保护效应。最近的多项研究发现,EPO及EPO-R广泛表达于多种恶性肿瘤细胞,EPO/EPO-R的自分泌/旁分泌通路与肿瘤微血管形成、刺激肿瘤细胞增殖、抑制凋亡及对放化疗的敏感性有关,确切机制需进一步研究。重组人促红细胞生成素(recombinant human erythropoietin,rh-EPO)在临床上已广泛用于治疗肿瘤相关贫血。研究证实其能增加血红蛋白水平,减少红细胞输注,同时改善患者生活质量。但亦有随机试验报道了rh-EPO治疗的患者相对安慰剂组患者无进展生存期下降。我们对EPO及其受体在非造血组织尤其是肿瘤组织中的表达、功能及相关机制的研究进展作简要概述。

Research advances in expression and functions of erythropoietin and erythropoietin receptor in cancers

Erythropoietin (EPO) has firstly known to regulate cell proliferation and differentiation along the erythroid lineage. Rencent studies have shown that EPO,a pleiotropic cytokine,is proangiogenic and exerts broad tissue-protective effects in diverse nonhematopoietic organs. A series of studies have documented the expression of EPO and EPO receptor (EPO-R) in various cancer cells. The presence of an autocrine-paracrine EPO/EPO-R system may associate with the potential for stimulation of tumor neoangiogenesis and tumor proliferation,inhibition of apoptosis,or modulation of sensitivity to chemoradiotherapy. The complex mechanism needs further research. Recombinant human erythropoietin (rh-EPO) has been widely used in clinic to treat malignancy-associated anemia. Clinical trials have documented the efficacy of rh-EPO in increasing hemoglobin levels,reducing red blood cell (RBC) transfusion requirements and improving quality of life in cancer patients. However,three randomized trials reported negative outcomes with rh-EPO,as patients in the rh-EPO arm fared worse than their placebo-treated counterparts with progression-free survival. This review described EPO and EPO-R biology,focusing on the expression,pleiotropic function and mechanism on nonhematopoietic tissues especially on cancer cells.