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Erythropoietin Stimulates Tumor Growth via EphB4.


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.

SUBMITTER: Pradeep S 

PROVIDER: S-EPMC4643364 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Erythropoietin Stimulates Tumor Growth via EphB4.

Pradeep Sunila S   Huang Jie J   Mora Edna M EM   Nick Alpa M AM   Cho Min Soon MS   Wu Sherry Y SY   Noh Kyunghee K   Pecot Chad V CV   Rupaimoole Rajesha R   Stein Martin A MA   Brock Stephan S   Wen Yunfei Y   Xiong Chiyi C   Gharpure Kshipra K   Hansen Jean M JM   Nagaraja Archana S AS   Previs Rebecca A RA   Vivas-Mejia Pablo P   Han Hee Dong HD   Hu Wei W   Mangala Lingegowda S LS   Zand Behrouz B   Stagg Loren J LJ   Ladbury John E JE   Ozpolat Bulent B   Alpay S Neslihan SN   Nishimura Masato M   Stone Rebecca L RL   Matsuo Koji K   Armaiz-Peña Guillermo N GN   Dalton Heather J HJ   Danes Christopher C   Goodman Blake B   Rodriguez-Aguayo Cristian C   Kruger Carola C   Schneider Armin A   Haghpeykar Shyon S   Jaladurgam Padmavathi P   Hung Mien-Chie MC   Coleman Robert L RL   Liu Jinsong J   Li Chun C   Urbauer Diana D   Lopez-Berestein Gabriel G   Jackson David B DB   Sood Anil K AK  

Cancer cell 20151017 5


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 ov  ...[more]

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