Combined effect of EPO and radiotherapy on the expression of endogenous molecular markers of tumor metabolism and metastasis.
Erythropoietin (EPO) has been used to correct cancer-related anemia and to improve tumor hypoxia, which both adversely affect the clinical condition of cancer patients and response to radiotherapy. Data available on the effects of EPO treatment in cancer are, however, conflicting. Several clinical studies investigating the influence of EPO treatment have given contradictory results as to whether or not this treatment positively influences survival. In light of these conflicting results, we studied the effects of EPO treatment either alone or in combination with radiotherapy on tumor oxygenation and on the expression pattern of several proteins related to tumor metabolism, survival, and spread in a rat colorectal cancer model. We found a statistically significant upregulation of hexokinase I, N-cadherin, and glucose transporter 3 when EPO treatment was combined with radiotherapy. Because these three proteins have distinct functions in protecting the cell in compromised conditions, these results indicate a detrimental role for the combination of EPO treatment and radiotherapy through the stimulation of tumor-cell metabolism, inhibition of apoptosis, and stimulation of tumor spread and seem to indicate that recombinant human EPO treatment negatively modulates radiotherapy efficacy.
Mees
Gilles
G
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Fonteyne
Philippe
P
Ceelen
Wim
W
Boterberg
Tom
T
Pauwels
Patrick
P
Vangestel
Christel
C
Van Damme
Nancy
N
Peeters
Marc
M
Dierckx
Rudi
R
Van De Wiele
Christophe
C
D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D003131:Combined Modality Therapy / Q000379:methods; D004921:Erythropoietin / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006400:Hematocrit; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D010100:Oxygen / Q000378:metabolism; D011878:Radiotherapy / Q000379:methods*; D051381:Rats; D016896:Treatment Outcome
D004921:Erythropoietin; D010100:Oxygen