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Erythropoietin Stimulates Tumor Growth via EphB4.

Authors :: Pradeep S
Huang J
Mora EM
Nick AM
Cho MS
Wu SY
Noh K
Pecot CV
Rupaimoole R
Stein MA
Brock S
Wen Y
Xiong C
Gharpure K
Hansen JM
Nagaraja AS
Previs RA
Vivas-Mejia P
Han HD
Hu W
Mangala LS
Zand B
Stagg LJ
Ladbury JE
Ozpolat B
Alpay SN
Nishimura M
Stone RL
Matsuo K
Armaiz-Peña GN
Dalton HJ
Danes C
Goodman B
Rodriguez-Aguayo C
Kruger C
Schneider A
Haghpeykar S
Jaladurgam P
Hung MC
Coleman RL
Liu J
Li C
Urbauer D
Lopez-Berestein G
Jackson DB
Sood AK
Source :: Cancer cell [Cancer Cell] 2015 Nov 09; Vol. 28 (5), pp. 610-622. Date of Electronic Publication: 2015 Oct 17.
Publication Year :: 2015
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.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)