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.
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Acknowledgments
We would like to thank Chemo Wanbang Biopharma Co. Ltd., Shanghai, for providing the rhEPO. This work was supported by project grants from the National Natural Science Foundation of China (Code 30572164, Code 30972715, Code 81371414).
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Ding, J., Li, QY., Yu, JZ. et al. The lack of CD131 and the inhibition of Neuro-2a growth by carbamylated erythropoietin. Cell Biol Toxicol 31, 29–38 (2015). https://doi.org/10.1007/s10565-015-9292-y
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DOI: https://doi.org/10.1007/s10565-015-9292-y