1. Erythropoietin Stimulates Tumor Growth via EphB4
- Author
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Shyon Haghpeykar, Jean M. Hansen, Rebecca L. Stone, Chiyi Xiong, Alpa M. Nick, Sunila Pradeep, Kshipra M. Gharpure, Gabriel Lopez-Berestein, Guillermo N. Armaiz-Pena, Mien Chie Hung, Chun Li, Edna M. Mora, Cristian Rodriguez-Aguayo, Sherry Y. Wu, Archana S. Nagaraja, Martin Stein, Hee Dong Han, Rebecca A. Previs, Anil K. Sood, Blake W. Goodman, Kyunghee Noh, Masato Nishimura, Robert L. Coleman, Armin Schneider, Min Soon Cho, Chad V. Pecot, Rajesha Rupaimoole, Jie Huang, Lingegowda S. Mangala, Bulent Ozpolat, Yunfei Wen, Jinsong Liu, Pablo E. Vivas-Mejia, Stephan Brock, Padmavathi Jaladurgam, John E. Ladbury, Diana L. Urbauer, Koji Matsuo, Heather J. Dalton, Carola Krüger, Christopher G. Danes, David B. Jackson, Loren J. Stagg, Wei Hu, Behrouz Zand, and S. Neslihan Alpay
- Subjects
Adult ,STAT3 Transcription Factor ,Cancer Research ,Blotting, Western ,Receptor, EphB4 ,Mice, Nude ,Breast Neoplasms ,Kaplan-Meier Estimate ,Article ,Young Adult ,Breast cancer ,Mediator ,Cell Line, Tumor ,hemic and lymphatic diseases ,Receptors, Erythropoietin ,medicine ,Animals ,Humans ,STAT3 ,Erythropoietin ,Aged ,Aged, 80 and over ,Ovarian Neoplasms ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Cancer ,Cell Biology ,Middle Aged ,medicine.disease ,Recombinant Proteins ,Erythropoietin receptor ,Gene Expression Regulation, Neoplastic ,Mice, Inbred C57BL ,Oncology ,Tumor progression ,Immunology ,Cancer cell ,Disease Progression ,MCF-7 Cells ,biology.protein ,Cancer research ,Female ,Protein Binding ,medicine.drug - Abstract
SummaryWhile 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.
- Published
- 2015
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