Erythropoietin (EPO) has no direct effect on tumor growth or angiogenesis in animal models.
9530 Background: Erythropoietin (EPO) increases tumor oxygenation in several pre-clinical models. This improvement in oxygenation should lead to enhanced treatment responses. However, EPO has failed to show improved treatment outcomes in 2 recent, randomized clinical trials involving non-anemic patients with head and neck and metastatic breast cancer. In this study we characterize the direct effects of EPO on tumor growth and angiogenesis in both breast and colorectal carcinoma. METHODS: Effects of EPO (Ortho Biotech, Raritan, NJ) on murine tumor growth (CT-26 and R3230) in over 200 non-anemic rodents randomized to either EPO or control was measured. EPO receptor expression was determined using standard IHC in both tumor types before and after treatment. Tumor proliferation, assessed by Ki-67 IHC staining, was also determined. In vivo angiogenesis was measured by vascular length density (VLD) and was calculated from intravital microscopy images of R3230 tumors grown in mammary window chambers. RESULTS: EPO increased the hematocrit significantly in all treated animals. Measured bidimensionally over the entire growth period, EPO had no effect on CT-26 or R3230 tumor growth at any time point. Both tumors expressed the EPO receptor. Ki-67 staining revealed no differences in proliferation between EPO-treated and control animals. In addition, angiogenesis was unaffected by systemic treatment with EPO. CONCLUSIONS: This study suggests that although EPO improves tumor oxygenation, this physiologic change is not attributable to either direct effects on tumor growth or angiogenesis. The cause for improvement in oxygenation remains under investigation. It is likely due to subtle changes in perfusion or tumor consumption that are not detected by simple vascular length density measurements. Besides its known effects on tumor oxygenation, other direct effects of EPO on tumor biology need to be examined. No significant financial relationships to disclose.
Hardee, ME; Kirkpatrick, JP; Snyder, S; Shan, S; Vujaskovic, Z; Rabbani, ZN; Dewhirst, MW; Blackwell, KL
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