title: Erythropoietin promotes the growth of pituitary adenomas by enhancing             angiogenesis.
abstract: rhEPO is frequently used in clinical practice to treat anemia. However,             recently rhEPO has been reported to accelerate tumor growth, progression and metastasis.             Many pituitary adenoma patients, particularly those with macroprolactinomas, tend             to have anemia and may need rhEPO therapy. To date, whether rhEPO has deleterious             effects on pituitary adenomas has not been defined. Here we demonstrated for the             first time that human pituitary adenomas are EPOR negative tumors and rhEPO accelerated             the tumor growth of MMQ pituitary adenoma xenografts via enhancement of angiogenesis             in vivo, whereas rhEPO displayed no direct effect on MMQ cells in vitro. Our mechanistic             study showed that rhEPO administration increased phosphorylation of JAK2, STAT3             and VEGF expression in human umbilical vein endothelial cells (HUVECs) in vitro             and in MMQ cell xenografts in vivo. Furthermore, VEGF inhibitor attenuated rhEPO             induced angiogenesis and delayed tumor growth in MMQ pituitary adenoma xenografts             in vivo. JAK2 inhibitor AG490 attenuated EPO induced HUVECs proliferation, phosphorylation             of JAK2, STAT3 and VEGF upregulation in vitro and inhibited EPO induced vessel             formation in Chicken chorioallantoic membrane (CAM) angiogenesis model in vivo.             These results suggest that rhEPO administration may promote the growth of pituitary             adenomas by enhancing angiogenesis through EPO-JAK2-STAT3-VEGF signaling pathway.             rhEPO should be used with caution in anemia patients bearing pituitary adenoma             due to its potential deleterious effects.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, PR China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Yang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Xuanmin
authors.initials: X
authors.lastname: Gu
authors.forename: Bo
authors.initials: B
authors.lastname: Fan
mesh_terms: D000293:Adolescent; D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D010911:Pituitary Neoplasms / Q000098:blood supply* / Q000473:pathology*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017467:Receptors, Erythropoietin / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D043925:Angiogenesis Inducing Agents; D017467:Receptors, Erythropoietin; C532610:tumonoic acid D; D004921:Erythropoietin; D011392:Proline
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