Erythropoietin Signaling Promotes Invasiveness of Human Head and Neck Squamous Cell Carcinoma

Neoplasia: An International Journal for Oncology Research

Ajay Verma¹  Ahmed Mohyeldin¹  Huasheng Lu¹  Clifton Dalgard¹  Stephen Y. Lai²  Noam Cohen³  Geza Acs⁴ 

[1] Department of Neurology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA;Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA;Department of Otorhinolaryngology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104;Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104;

关键词: Erythropoietin;    HIF;    cancer;    invasion;    hypoxia;   

DOI  :  10.1593/neo.04685

来源: DOAJ

【 摘 要 】

Erythropoietin (Epo) is used for managing anemia in cancer patients. However, recent studies have raised concerns for this practice. We investigated the expression and function of Epo and the erythropoietin receptor (EpoR) in tumor biopsies and cell lines from human head and neck cancer. Epo responsiveness of the cell lines was assessed by Epoetin-α-induced tyrosine phosphorylation of the Janus kinase 2 (JAK2) protein kinase. Transmigration assays across Matrigel-coated filters were used to examine the effects of Epoetin-A on cell invasiveness. In 32 biopsies, we observed a significant association between disease progression and expression of Epo and its receptor, EpoR. Expression was highest in malignant cells, particularly within hypoxic and infiltrating tumor regions. Although both Epo and EpoR were expressed in human head and neck carcinoma cell lines, only EpoR was upregulated by hypoxia. Epoetin-α treatment induced prominent JAK2 phosphorylation and enhanced cell invasion. Inhibition of JAK2 phosphorylation reduced both basal and Epo-induced invasiveness. Our findings support a role for autocrine or paracrine Epo signaling in the malignant progression and local invasiveness of head and neck cancer. This mechanism may also be activated by recombinant Epo therapy and could potentially produce detrimental effects in rhEpo-treated cancer patients.

【 授权许可】

Unknown