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Transl Oncol. 2010 Jun 1;3(3):176-80.

Limitations of a murine transgenic breast cancer model for studies of erythropoietin-induced tumor progression.

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  • 1Department of Medicine/Hematology and the Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.

Abstract

Adverse effects of erythropoietin (EPO) on tumor progression and survival were observed in recent phase 3 oncology trials. However, mechanisms remain poorly understood. We tested the effects of exogenous EPO on murine B16F10 melanoma growth in a subcutaneous tumor transplant model, and for the first time, in a model of spontaneous tumor formation within autochthonous epithelial tissues using murine mammary tumor virus promoter polyoma virus middle T antigen (MMTV-PyMT) transgenic mice. EPO receptor (EPOR) messenger RNA (mRNA) was detectable in both B16F10 tumors and mammary tumors from MMTV-PyMT mice but was 0.12 +/- 0.02% and 1.3 +/- 0.91% of the EPOR mRNA level in murine erythroid HCD-57 cells, respectively. B16F10 tumor growth rates in mice treated for 3 weeks with 30 microg/kg per week of darbepoetin alpha, 0.41 inverse days (range, 0.05-0.69 inverse days; n = 16), were similar to tumor growth rates observed in mice treated with PBS, 0.42 inverse days (range, 0.10-0.69 inverse days; n = 17). In contrast, darbepoetin alpha raised hematocrit levels to 0.593 (maximum, 0.729) compared with 0.448 (maximum, 0.532) in PBS-treated mice (P = .0004). In MMTV-PyMT mice, the weights of tumor-bearing mammary glands in mice treated for 6 weeks with 30 microg/kg per week of darbepoetin alpha, 3.37 g (range, 1.94-5.81 g; n = 27), did not significantly differ from the weights in PBS-treated mice, 3.76 g (range, 2.30-6.33 g; n = 26). In contrast, darbepoetin alpha raised hematocrit levels to 0.441 (maximum, 0.606) compared with 0.405 (maximum, 0.492) in PBS-treated mice (P = .05). Thus, effects of exogenous EPO on tumor growth were not recapitulated in these murine tumor models.

PMID:
20563259
[PubMed]
PMCID:
PMC2887647
Free PMC Article

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