Erythropoietin: A Hormone with Multiple Functions

Erythropoietin (EPO), the main hemopoietic hormone synthesized by the kidney as well as by the liver in fetal life, is implicated in mammalian erythropoiesis. Production and secretion of EPO and the expression of its receptor (EPO-R) are regulated by tissue oxygenation. EPO and EPO-R, expressed in several tissues, exert pleiotropic activities and have different effects on nonhemopoietic cells. EPO is a cytokine with antiapoptotic activity and plays a potential neuroprotective and cardioprotective role against ischemia. EPO is also involved in angiogenesis, neurogenesis, and the immune response. EPO can prevent metabolic alterations, neuronal and vascular degeneration, and inflammatory cell activation. Consequently, EPO may be of therapeutic use for a variety of disorders. Many tumors express EPO and/or EPO-R, but the action of EPO on tumor cells remains controversial. It has been suggested that EPO promotes the proliferation and survival of cancer cells expressing EPO-R. On the other hand, other reports have concluded that EPO-R plays no role in tumor progression. This review provides a detailed insight into the nonhemopoietic role of EPO and its mechanism(s) of action which may lead to a better understanding of its potential therapeutic value in diverse clinical settings.