Sunila Pradeep 1 , Jie Huang 1 , Edna M Mora 2 , Alpa M Nick 1 , Min Soon Cho 3 , Sherry Y Wu 1 , Kyunghee Noh 1 , Chad V Pecot 4 , Rajesha Rupaimoole 1 , Martin A Stein 5 , Stephan Brock 5 , Yunfei Wen 1 , Chiyi Xiong 6 , Kshipra Gharpure 1 , Jean M Hansen 1 , Archana S Nagaraja 1 , Rebecca A Previs 1 , Pablo Vivas-Mejia 7 , Hee Dong Han 8 , Wei Hu 1 , Lingegowda S Mangala 8 , Behrouz Zand 1 , Loren J Stagg 9 , John E Ladbury 9 , Bulent Ozpolat 10 , S Neslihan Alpay 10 , Masato Nishimura 1 , Rebecca L Stone 1 , Koji Matsuo 1 , Guillermo N Armaiz-Peña 1 , Heather J Dalton 1 , Christopher Danes 1 , Blake Goodman 1 , Cristian Rodriguez-Aguayo 10 , Carola Kruger 11 , Armin Schneider 11 , Shyon Haghpeykar 1 , Padmavathi Jaladurgam 1 , Mien-Chie Hung 12 , Robert L Coleman 1 , Jinsong Liu 13 , Chun Li 9 , Diana Urbauer 14 , Gabriel Lopez-Berestein 15 , David B Jackson 5 , Anil K Sood 16
Nov 9 2015
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.