title: Human recombinant erythropoietin (rEpo) has no effect on tumour growth or angiogenesis.
abstract: Tumour hypoxia has been shown to increase mutation rate, angiogenesis, and metastatic potential, and decrease response to conventional therapeutics. Improved tumour oxygenation should translate into increased treatment response. Exogenous recombinant erythropoietin (rEpo) has been recently shown to increase tumour oxygenation in a mammary carcinoma model. The mechanism of this action is not yet understood completely. The presence of Epo and its receptor (EpoR) have been demonstrated on several normal and neoplastic tissues, including blood vessels and various solid tumours. In addition, rEpo has been shown in two recent prospective, randomized clinical trials to negatively impact treatment outcome. In this study, we attempt to characterize the direct effects of rEpo on tumour growth and angiogenesis in two separate rodent carcinomas. The effect of rEpo on R3230 rat mammary adenocarcinomas, CT-26 mouse colon carcinomas, HCT-116 human colon carcinomas, and FaDu human head and neck tumours, all of which express EpoR, was examined. There were no differences in tumour growth or proliferation (measured by Ki-67) between placebo-treated and rEpo-treated tumours. In the mammary window chamber, vascular length density (VLD) measurements in serial images of both placebo-treated and Epo-treated rats revealed no difference in angiogenesis between the Epo-treated tumours and placebo-treated tumours at any time point. These experiments are important because they suggest that the recent clinical detriment seen with the use of Epo is not due to its tumour growth effects or angiogenesis. These studies also suggest that further preclinical studies need to examine rEpo's direct tumour effects in efforts to improve the therapeutic benefits of Epo in solid tumour patients.
authors.affiliation: Department of Pathology, Duke University Medical Center, Box 3893, Durham, NC 27710, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Hardee
authors.forename: J P
authors.initials: JP
authors.lastname: Kirkpatrick
authors.forename: S
authors.initials: S
authors.lastname: Shan
authors.forename: S A
authors.initials: SA
authors.lastname: Snyder
authors.forename: Z
authors.initials: Z
authors.lastname: Vujaskovic
authors.forename: Z N
authors.initials: ZN
authors.lastname: Rabbani
authors.forename: M W
authors.initials: MW
authors.lastname: Dewhirst
authors.forename: K L
authors.initials: KL
authors.lastname: Blackwell
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000473:pathology*; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology*; D004921:Erythropoietin / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D051379:Mice; D009389:Neovascularization, Pathologic; D010919:Placebos; D011897:Random Allocation; D051381:Rats; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
chemical_list: D010919:Placebos; D011994:Recombinant Proteins; D004921:Erythropoietin