State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou, China.
The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, Guizhou, China.
Adv Exp Med Biol. 2020;1223:17-30. doi: 10.1007/978-3-030-35582-1_2.
Erythropoietin (EPO), the primary cytokine of erythropoiesis, stimulates both proliferation and differentiation of erythroid progenitors and their maturation to red blood cells. Basal EPO levels maintain the optimum levels of circulating red blood cells. However, during hypoxia, EPO secretion and its expression is elevated drastically in renal interstitial fibroblasts, thereby increasing the number of erythroid progenitors and accelerating their differentiation to mature erythrocytes. A tight regulation of this pathway is therefore of paramount importance. The biological response to EPO is commenced through the involvement of its cognate receptor, EPOR. The receptor-ligand complex results in homodimerization and conformational changes, which trigger downstream signaling events and cause activation or inactivation of critical transcription factors that promote erythroid expansion. In recent years, recombinant human EPO (rEPO) has been widely used as a therapeutic tool to treat a number of anemias induced by infection, and chemotherapy for various cancers. However, several studies have uncovered a tumor promoting ability of EPO in man, which likely occurs through EPOR or alternative receptor(s). On the other hand, some studies have demonstrated a strong anticancer activity of EPO, although the mechanism still remains unclear. A thorough investigation of EPOR signaling could yield enhanced understanding of the pathobiology for a variety of disorders, as well as the potential novel therapeutic strategies. In this chapter, in addition to the clinical relevance of EPO/EPOR signaling, we review its anticancer efficacy within various tumor microenvironments.
促红细胞生成素（EPO）是红细胞生成的主要细胞因子，它刺激红系祖细胞的增殖和分化及其向成熟红细胞的成熟。基础 EPO 水平维持循环红细胞的最佳水平。然而，在缺氧的情况下，肾间质成纤维细胞中 EPO 的分泌和表达会急剧增加，从而增加红系祖细胞的数量，并加速其向成熟红细胞的分化。因此，对这条途径进行严格的调节至关重要。EPO 的生物学反应是通过其同源受体 EPOR 的参与开始的。受体-配体复合物导致同源二聚体化和构象变化，从而触发下游信号事件，并导致激活或失活促进红细胞扩张的关键转录因子。近年来，重组人促红细胞生成素（rEPO）已被广泛用作治疗由感染和各种癌症化疗引起的多种贫血的治疗工具。然而，几项研究已经揭示了 EPO 在人类中的促肿瘤能力，这可能是通过 EPOR 或替代受体（s）发生的。另一方面，一些研究已经证明了 EPO 具有很强的抗癌活性，尽管其机制仍不清楚。对 EPOR 信号的深入研究可以增强对各种疾病的病理生物学的理解，以及潜在的新的治疗策略。在本章中，除了 EPO/EPOR 信号的临床相关性外，我们还综述了其在各种肿瘤微环境中的抗癌功效。
