Recombinant erythropoietin differently affects proliferation of mesothelioma cells but not sensitivity to cisplatin and pemetrexed.
The combination of cisplatin and pemetrexed represents the newly established standard of care for patients with unresectable malignant mesothelioma (MM). However, this chemotherapy regimen appears to be associated with an increased prevalence of higher grade anemia as compared to treatment with cisplatin alone. Human recombinant erythropoietin (rHuEpo) is currently used for the treatment of anemia in cancer patients. Still, following the finding that the erythropoietin receptor (EpoR) is expressed by several tumor cells types and after the trials reporting that the recombinant cytokine can adversely affect tumor progression and patient survival, the clinical safety of rHuEpo administration to neoplastic patients has recently been questioned. The observation that the expression of EpoR, variably associated with the expression of the cognate ligand, is a common feature of MM cells prompted us to investigate whether treatment with rHuEpo could elicit proliferative and cytoprotective signals in EpoR-positive MM cell lines. Biochemical responsiveness of MM cells to rHuEpo was demonstrated by the time-course activation of both ERK1/2 and AKT following treatment with the recombinant cytokine. A moderately increased mitogenic activity was observed in two out of five MM cell lines treated with pharmacologically relevant concentrations of rHuEpo. On the other hand, the recombinant cytokine, administered either before or after cisplatin and pemetrexed, failed to interfere with the cytotoxic effects exerted by the chemotherapeutic drugs on the five MM cell lines. According to the presented findings, rHuEpo appears to have an overall limited impact on cell growth and no effect on MM sensitivity to chemotherapy.
Palumbo
Camilla
C
Department of Experimental Medicine and Biochemical Sciences, Università degli Studi di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. camilla.palumbo@uniroma2.it
Battisti
Sonia
S
Carbone
Daniela
D
Albonici
Loredana
L
Alimandi
Maurizio
M
Bei
Roberto
R
Modesti
Andrea
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004347:Drug Interactions; D004921:Erythropoietin / Q000494:pharmacology*; D015870:Gene Expression; D005971:Glutamates / Q000494:pharmacology*; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D008654:Mesothelioma / Q000188:drug therapy*; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D000068437:Pemetrexed; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins
D000970:Antineoplastic Agents; D005971:Glutamates; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; C103998:epoetin beta; D000068437:Pemetrexed; D004921:Erythropoietin; D006147:Guanine; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002945:Cisplatin