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  • Original Paper
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Erythropoietin-mediated activation of JAK-STAT signaling contributes to cellular invasion in head and neck squamous cell carcinoma

Oncogene volume 24, pages 4442–4449 (2005)Cite this article

A Corrigendum to this article was published on 08 December 2005

Abstract

Originally characterized as a growth factor for erythrocytes, erythropoietin (EPO) is used to treat anemia and fatigue in cancer patients receiving radiation therapy and chemotherapy. EPO and the EPO receptor (EPOR) are expressed in nonhematopoietic cells and cancers. However, the role of EPO and EPOR within nonhematopoietic cancer cells remains incompletely understood. Although a recent clinical trial demonstrated worse tumor control and survival in head and neck cancer patients treated with EPO, the role of EPO and EPOR in head and neck squamous cell carcinoma (HNSCC) has not been examined. In the present study, we demonstrate the previously unrecognized EPO-mediated invasion by HNSCC cells through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. Furthermore, we confirmed the expression of EPO and EPOR in a panel of human HNSCC cell lines and tissue specimens. Pharmacological doses of EPO also had a limited proliferation effect in these cell lines. These results define a novel role for EPO in mediating tumor cell invasion. Increased levels of EPO and EPOR in lymph node metastases as compared to primary tumors from HNSCC patients further support the role of EPO/EPOR in HNSCC disease progression and metastasis.

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Acknowledgements

The authors thank Jonas T Johnson, Rebecca E Fraioli and Charles J Lin for critically reviewing this manuscript. This research was supported in part through the Young Clinical Scientist Award from the Flight Attendant Medical Research Institute (SYL), a National Institutes of Health T32 training grant (DC000066-01A2) and the Stout Family Fund for Head and Neck Cancer Research at the Eye & Ear Foundation of Pittsburgh.

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  1. Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

Authors and Affiliations

  1. Department of Otolaryngology – Head and Neck Surgery, The Eye & Ear Institute, University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA

    Stephen Y Lai, Erin E Childs, Sichuan Xi, Francesca M Coppelli, Robert L Ferris & Jennifer R Grandis

  2. Department of Immunology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA

    Robert L Ferris

  3. Department of Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA

    Alan Wells

  4. Department of Pharmacology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA

    Jennifer R Grandis

  5. University of Pittsburgh School of Medicine and Biostatistics Facility, University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA

    William E Gooding

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Lai, S., Childs, E., Xi, S. et al. Erythropoietin-mediated activation of JAK-STAT signaling contributes to cellular invasion in head and neck squamous cell carcinoma. Oncogene 24, 4442–4449 (2005). https://doi.org/10.1038/sj.onc.1208635

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