| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Human Cancer Biology |
1 Department of Medicine, Duke University School of Medicine, Durham, North Carolina; 2 Biosciences Division, SRI International, Menlo Park, California; and 3 Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
Requests for reprints: Murat O. Arcasoy, Divisions of Hematology and Medical Oncology, Department of Medicine, Duke University School of Medicine, DUMC Box 3912, Durham, NC 27710. Phone: 919-668-6309; Fax: 919-681-6160; E-mail: arcas001{at}mc.duke.edu
Purpose: Erythropoietin, an oxygen-regulated glycoprotein hormone, is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor [erythropoietin receptor (EPOR)]. The recombinant form of human erythropoietin is used to prevent or treat anemia in cancer patients. However, in a recent randomized, placebo-controlled trial involving patients receiving curative radiotherapy for squamous cell carcinoma of the head and neck, erythropoietin treatment was associated with poorer locoregional progression-free survival. The purpose of our study was to determine whether EPOR and its ligand erythropoietin are expressed in primary head and neck cancer. We also investigated the hypothesis that erythropoietin expression in malignant cells may be associated with the presence of tumor hypoxia, an important factor involved in resistance to radiation treatment, tumor aggressiveness, and poor prognosis.
Experimental Design: Twenty-one patients received an i.v. infusion of the hypoxia marker pimonidazole hydrochloride before multiple tumor biopsies. Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for EPOR and erythropoietin expression and pimonidazole binding.
Results: EPOR expression was present in tumor cells in 97% of the biopsies. Coexpression of erythropoietin was observed in 90% of biopsies. Erythropoietin and pimonidazole adduct staining did not always colocalize within tumors, but there was a significant positive correlation between levels of microregional erythropoietin expression and pimonidazole binding.
Conclusions: The coexpression of erythropoietin and EPOR in tumor cells suggests that erythropoietin may potentially function as an autocrine or paracrine factor in head and neck cancer. The expression of the hypoxia-inducible protein erythropoietin in tumor cells correlates with levels of tumor hypoxia.
Key Words: cytokine receptor • oxygen regulation • pimonidazole • squamous cell carcinoma
This article has been cited by other articles:
|
|
 |
|
  S. N. Hamadmad and R. J. Hohl Erythropoietin Stimulates Cancer Cell Migration and Activates RhoA Protein through a Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase-Dependent Mechanism J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1227 - 1233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Saintigny, B. Besse, P. Callard, A.-C. Vergnaud, S. Czernichow, M. Colombat, P. Girard, P. Validire, J.-L. Breau, J.-F. Bernaudin, et al. Erythropoietin and Erythropoietin Receptor Coexpression Is Associated with Poor Survival in Stage I Non Small Cell Lung Cancer Clin. Cancer Res., August 15, 2007; 13(16): 4825 - 4831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kokhaei, A. O. Abdalla, L. Hansson, E. Mikaelsson, M. Kubbies, A. Haselbeck, H. Jernberg-Wiklund, H. Mellstedt, and A. Osterborg Expression of Erythropoietin Receptor and In vitro Functional Effects of Epoetins in B-Cell Malignancies Clin. Cancer Res., June 15, 2007; 13(12): 3536 - 3544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zeuner, M. Signore, D. Martinetti, M. Bartucci, C. Peschle, and R. De Maria Chemotherapy-Induced Thrombocytopenia Derives from the Selective Death of Megakaryocyte Progenitors and Can Be Rescued by Stem Cell Factor Cancer Res., May 15, 2007; 67(10): 4767 - 4773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. M. Brown, P. Maxwell, A. N.J. Graham, A. Yakkundi, E. A. Dunlop, Z. Shi, P. G. Johnston, and T. R.J. Lappin Erythropoietin Receptor Expression in Non-Small Cell Lung Carcinoma: A Question of Antibody Specificity Stem Cells, March 1, 2007; 25(3): 718 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Leo, L.-C. Horn, C. Rauscher, B. Hentschel, A. Liebmann, G. Hildebrandt, and M. Hockel Expression of Erythropoietin and Erythropoietin Receptor in Cervical Cancer and Relationship to Survival, Hypoxia, and Apoptosis Clin. Cancer Res., December 1, 2006; 12(23): 6894 - 6900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Henke, D. Mattern, M. Pepe, C. Bezay, C. Weissenberger, M. Werner, and F. Pajonk Do Erythropoietin Receptors on Cancer Cells Explain Unexpected Clinical Findings? J. Clin. Oncol., October 10, 2006; 24(29): 4708 - 4713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Henke, A. Verma, G. Acs, S. Elliott, L. Busse, C. Spahr, and A. M. Sinclair Erythropoietin receptors on cancer cells: exciting perspectives, difficult to appreciate Blood, August 1, 2006; 108(3): 1107 - 1109. [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Laderoute, K. Amin, J. M. Calaoagan, M. Knapp, T. Le, J. Orduna, M. Foretz, and B. Viollet 5'-AMP-Activated Protein Kinase (AMPK) Is Induced by Low-Oxygen and Glucose Deprivation Conditions Found in Solid-Tumor Microenvironments. Mol. Cell. Biol., July 1, 2006; 26(14): 5336 - 5347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bohlius, J. Wilson, J. Seidenfeld, M. Piper, G. Schwarzer, J. Sandercock, S. Trelle, O. Weingart, S. Bayliss, B. Djulbegovic, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst, May 17, 2006; 98(10): 708 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Elliott, L. Busse, M. B. Bass, H. Lu, I. Sarosi, A. M. Sinclair, C. Spahr, M. Um, G. Van, and C. G. Begley Anti-Epo receptor antibodies do not predict Epo receptor expression Blood, March 1, 2006; 107(5): 1892 - 1895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. LaMontagne, J. Butler, D. J. Marshall, J. Tullai, Z. Gechtman, C. Hall, A. Meshaw, and F. X. Farrell Recombinant epoetins do not stimulate tumor growth in erythropoietin receptor-positive breast carcinoma models. Mol. Cancer Ther., February 1, 2006; 5(2): 347 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Hardee, M. O. Arcasoy, K. L. Blackwell, J. P. Kirkpatrick, and M. W. Dewhirst Erythropoietin Biology in Cancer Clin. Cancer Res., January 15, 2006; 12(2): 332 - 339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Erovic, M. Pelzmann, M. Ch. Grasl, J. Pammer, G. Kornek, W. Brannath, E. Selzer, and D. Thurnher Mcl-1, Vascular Endothelial Growth Factor-R2, and 14-3-3{sigma} Expression Might Predict Primary Response against Radiotherapy and Chemotherapy in Patients with Locally Advanced Squamous Cell Carcinomas of the Head and Neck Clin. Cancer Res., December 15, 2005; 11(24): 8632 - 8636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Winter, K. A. Shah, L. Campo, H. Turley, R. Leek, R. J. Corbridge, G. J. Cox, and A. L. Harris Relation of Erythropoietin and Erythropoietin Receptor Expression to Hypoxia and Anemia in Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., November 1, 2005; 11(21): 7614 - 7620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Maiese, F. Li, and Z. Z. Chong Erythropoietin and Cancer--Reply JAMA, April 20, 2005; 293(15): 1858 - 1859. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Cell Growth & Differentiation |
