Erythropoietin Stimulates Tumor Growth via EphB4

Sunila Pradeep, Jie Huang, Edna M. Mora, Alpa M. Nick, Min Soon Cho, Sherry Y. Wu, Kyunghee Noh, Chad V. Pecot, Rajesha Rupaimoole, Martin A. Stein, Stephan Brock, Yunfei Wen, Chiyi Xiong, Kshipra Gharpure, Jean M. Hansen, Archana S. Nagaraja, Rebecca A. Previs, Pablo Vivas-Mejia, Hee Dong Han, Wei Hu, Lingegowda S. Mangala, Behrouz Zand, Loren J. Stagg, John E. Ladbury, Bulent Ozpolat, S. Neslihan Alpay, Masato Nishimura, Rebecca L. Stone, Koji Matsuo, Guillermo N. Armaiz-Peña, Heather J. Dalton, Christopher Danes, Blake Goodman, Cristian Rodriguez-Aguayo, Carola Kruger, Armin Schneider, Shyon Haghpeykar, Padmavathi Jaladurgam, Mien-Chie Hung, Robert L. Coleman, Jinsong Liu, Chun Li, Diana Urbauer, Gabriel Lopez-Berestein, David B. Jackson, Anil K. Sood

Cancer Cell
2015 vol: 28 issue: 5 pp: 610-622 doi: 10.1016/j.ccell.2015.09.008

Abstract
While recombinant human erythropoietin (rhEpo) has been widely used to treat anemia in cancer patients, concerns about its adverse effects on patient survival have emerged. A lack of correlation between expression of the canonical EpoR and rhEpo’s effects on cancer cells prompted us to consider the existence of an alternative Epo receptor. Here, we identified EphB4 as an Epo receptor that triggers downstream signaling via STAT3 and promotes rhEpo-induced tumor growth and progression. In human ovarian and breast cancer samples, expression of EphB4 rather than the canonical EpoR correlated with decreased disease-specific survival in rhEpo-treated patients. These results identify EphB4 as a critical mediator of erythropoietin-induced tumor progression and further provide clinically significant dimension to the biology of erythropoietin.

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Topics: Peptides, SPR, Monolith – MicroScale Thermophoresis, MST, Proteins, Publications