Preclinical studies of erythropoietin receptor expression in tumour cells: impact on clinical use of erythropoietic proteins to correct cancer-related anaemia.
In vitro and animal model studies have shown erythropoietin receptor (Epo-R) mRNA and/or protein may be present in a range of human tumours and cancer cell lines, and erythropoiesis-stimulating agents (ESAs) have been reported to have tumour cell growth-modulating effects. Following a review of the literature, we conclude that considerations must be made when interpreting data from the preclinical studies. First, supraphysiological doses of ESAs were usually used. Second, there are no well validated, commercially available antibodies for identifying the presence and functionality of Epo-R at the protein level, either intracellularly or on the cell surface. Data from previous studies that used antibodies only for Epo-R detection must therefore be interpreted with caution. Together with diverging results in the literature, these methodological limitations indicate that findings from preclinical studies must not be over-translated in terms of their clinical relevance to patients with cancer.
Osterborg
Anders
A
Department of Oncology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. anders.osterborg@karolinska.se
Aapro
Matti
M
Cornes
Paul
P
Haselbeck
Anton
A
Hayward
Colin R W
CR
Jelkmann
Wolfgang
W
D000740:Anemia / Q000188:drug therapy*; D015687:Cell Hypoxia; D018450:Disease Progression; D004341:Drug Evaluation; D004920:Erythropoiesis; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000150:complications* / Q000473:pathology; D009389:Neovascularization, Pathologic; D017467:Receptors, Erythropoietin / Q000378:metabolism*
D017467:Receptors, Erythropoietin; D004921:Erythropoietin