title: The lack of CD131 and the inhibition of Neuro-2a growth by carbamylated erythropoietin.
abstract: Recombinant human erythropoietin (EPO), a glycohormone, is one of the leading biopharmaceutical products, while carbamylated erythropoietin (CEPO), an EPO derivative, is attracting widespread interest due to its neuroprotective effects without erythropoiesis in several cells and animal models. However, exogenous EPO promotes an angiogenic response from tumor cells and is associated with tumor growth, but knowledge of CEPO on tumor growth is lacking. Here we show that CEPO, but not EPO, inhibited Neuro-2a growth and viability. As expected, CEPO--unlike EPO--did not activate JAK-2 either in primary neurons or in Neuro-2a cells. Interestingly, CEPO did not induce GDNF expression and subsequent AKT activation in Neuro-2a cells. Before CEPO/EPO treatment, glial cell line-derived neurotrophic factor (GDNF) neutralization and GFR receptor blocking decreased the viability of EPO-treated Neuro-2a cells but did not influence CEPO-treated Neuro-2a cells. As compared to primary neurons, the expression of CD131, as a receptor complex binding to CEPO, is almost lacking in Neuro-2a cells. In BABL/C-nu mice, CEPO did not promote the growth of Neuro-2a cells nor extended the survival time compared to mice treated with EPO. The results indicate that CEPO did not promote tumor growth because of lower expression of CD131 and subsequent dysfunction of CD131/GDNF/AKT pathway in Neuro-2a cells, revealing its therapeutic potential in future clinical application.
authors: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 12 Middle Wulumuqi Road, 200040, Shanghai, China.
authors: Jing
authors: J
authors: Ding
authors: Qin-Ying
authors: QY
authors: Li
authors: Jie-Zhong
authors: JZ
authors: Yu
authors: Xin
authors: X
authors: Wang
authors: Chuan-Zhen
authors: CZ
authors: Lu
authors: Cun-Gen
authors: CG
authors: Ma
authors: Bao-Guo
authors: BG
authors: Xiao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D053648:Cytokine Receptor Common beta Subunit / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis; D053614:Janus Kinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation
chemical_list: D053648:Cytokine Receptor Common beta Subunit; D051100:Glial Cell Line-Derived Neurotrophic Factor; C488171:carbamylated erythropoietin; D004921:Erythropoietin; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2