Impact of erythropoietin on the effects of irradiation under hypoxia.
OBJECTIVE
Head and neck squamous cell carcinoma (HNSCC) represents an ideal model for assessing the impact of anemia and tumor hypoxia on the response to radiotherapy (RT). Various treatment strategies aimed at increasing tumor oxygenation in HNSCC patients have been studied and these studies have been fueled by evidence that hypoxia and, unexpectedly, erythropoietin (EPO), adversely affect the radiosensitivity of cells. The purpose of the present study was to experimentally examine the relationship between hypoxia, EPO, its receptor EPOR, EGFR and their effects on the survival and radiosensitivity of HNSCC cells underwent hypoxia.


METHODS
We used Cal-166 head and neck cell line to investigate different cellular responses after RT given in oxic and hypoxic conditions, focusing on the role of EPO administration in cell proliferation and in regulating response to RT.


RESULTS
Our results show that EPO do not evoke a physiologic response on EPOR-bearing tumor cells as assessed by cellular growth and proliferation. In addition, we present some indications that EPO could activate opposite signals related to proliferation, DNA repair and apoptosis. Among them, EGFR and AKT phosphorylation may play a role in radioresistance.


CONCLUSIONS
We concluded that the expression of the EPOR in Cal-166 cells does not seem essential for their growth and that administration of EPO does not affect RT efficacy.
Lo Nigro
Cristiana
C
Laboratorio di Oncologia Translazionale, SC Oncologia, ASO S. Croce e Carle, 12100 Cuneo, Italy. lonigro.c@ospedale.cuneo.it
Maffi
Monica
M
Fischel
Jean Louis
JL
Monteverde
Martino
M
Catarsi
Paolo
P
Tonissi
Federica
F
Lattanzio
Laura
L
Riba
Michela
M
Etienne-Grimaldi
Marie-Christine
MC
Formento
Patricia
P
Milano
Gerard
G
Merlano
Marco
M
D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D019610:Cytoprotection; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000502:physiology; D066246:ErbB Receptors / Q000032:analysis; D004921:Erythropoietin / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D017467:Receptors, Erythropoietin / Q000032:analysis; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D017467:Receptors, Erythropoietin; D000076105:X-ray Repair Cross Complementing Protein 1; D004921:Erythropoietin; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt