Human recombinant erythropoietin does not promote cancer growth in presence of functional receptors expressed in cancer cells.
Human recombinant erythropoietin (hrEPO) therapy might be associated with tumor progression and death. This effect has been suggested to be secondary to rhEPO binding to its receptor (EPOR) expressed on cancer cells. However, there are several concerns about EPOR functionality when expressed on cancer cells. In this paper we have provided evidence that EPOR expressed in cancer cells could be implicated in proliferation events because a transfection of EPOR siRNA to EPOR-expressing bladder cancer cells resulted in a marked reduction in cell growth. However, these cell lines do not grow in the presence of hrEPO. Furthermore, bladder cancer patients that expressed EPOR in tumor samples had a reduced survival in absence of rhEPO treatment. Therefore, EPOR is implicated in bladder cancer growth but this effect appears to be independent from rhEPO supplementation. Reports which suggest that rhEPO promotes cancer growth due to the expression of EPOR in cancer cells must be observed with caution since in the presence of functional EPOR rhEPO does not promote growth.
Belda-Iniesta
Cristóbal
C
Translational Oncology Unit (CSIC/UAM), Medical Oncology Division, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain. cbelda@iib.uam.es
Perona
Rosario
R
Carpeño
Javier de Castro
Jde C
Cejas
Paloma
P
Casado
Enrique
E
Manguan-García
Cristina
C
Ibanez de Caceres
Inmaculada
I
Sanchez-Perez
Isabel
I
Andreu
Francisco Bernabeu
FB
Ferreira
Javier Alves
JA
Aguilera
Alfredo
A
de la Peña
Javier
J
Perez-Sánchez
Elia
E
Madero
Rosario
R
Feliu
Jaime
J
Sereno
María
M
González-Barón
Manuel
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000819:agonists / Q000032:analysis / Q000378:metabolism*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D004921:Erythropoietin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017467:Receptors, Erythropoietin / Q000819:agonists / Q000032:analysis / Q000378:metabolism*; D011994:Recombinant Proteins; D012189:Retrospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
D014408:Biomarkers, Tumor; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin