Recombinant Human Erythropoietin Alpha Improves the Efficacy of Radiotherapy of a Human Tumor Xenograft, Affecting Tumor Cells and Microvessels
Abstract
Background and purpose Tumor-induced anemia often occurs in cancer patients, and is corrected by recombinant human erythropoietins (rHuEPOs). Recent studies indicated that, besides erythroid progenitor cells, tumor and endothelial cells express erythropoietin receptor (EPOR) as well; therefore, rHuEPO may affect their functions. Here, the effect of rHuEPOalpha on irradiation in EPOR-positive human squamous cell carcinoma xenograft was tested.Material and methods A431 tumor-bearing SCID mice were treated from the tumor implantation with rHuEPOalpha at human-equivalent dose. Xenografts were irradiated (5 Gy) on day 14, and the final tumor mass was measured on day 22. The systemic effects of rHuEPOalpha on the hemoglobin level, on tumor-associated blood vessels and on hypoxia-inducible factor-(HIF-)1alpha expression of the tumor xenografts were monitored. The proliferation, apoptosis and clonogenic capacity of A431 cancer cells treated with rHuEPOalpha and irradiation were also tested in vitro.Results In vitro, rHuEPOalpha treatment alone did not modify the proliferation of EPOR-positive A431 tumor cells but enhanced the effect of irradiation on proliferation, apoptosis and clonogenic capacity. In vivo, rHuEPOalpha administration compensated the tumor-induced anemia in SCID mice and decreased tumoral HIF-1alpha expression but had no effect on tumor growth. At the same time rHuEPOalpha treatment significantly increased the efficacy of radiotherapy in vivo (tumor weight of 23.9 +/- 4.7 mg and 34.9 +/- 4.6 mg, respectively), mediated by increased tumoral blood vessel destruction.Conclusion rHuEPOalpha treatment may modulate the efficacy of cancer radiotherapy not only by reducing systemic hypoxia and tumoral HIF-1alpha expression, but also by destroying tumoral vessels.
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Erythropoiesis stimulating agent (ESA) treatment may promote the efficacy of radiotherapy, as observed in preclinical models.
“promoting efficacy of radiotherapy [81], asx observed in preclinical models.”
From Hypoxia Signaling in Cancer: From Basics to Clinical Practice (2021) · cites this paper as [81]
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Hypoxia Signaling in Cancer: From Basics to Clinical Practice
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- Authors
- Lövey, J., Bereczky, B., Gilly, R., Kenessey, I., Rásó, E., Simon, E., Dobos, J., Vágó, Á., Kásler, M., Döme, B., Tímár, J., & Tóvári, J.
- Affiliations
- National Institute of Oncology (HU)
- Országos Korányi Tbc és Pulmonológiai Intézet (HU)
- Semmelweis University (HU)
- Corresponding author
- Tóvári, József
- ORCID
- Venue
- Strahlentherapie und Onkologie
- Published
- 2008-01
- Volume
- 184
- Issue
- 1
- Pages
- 1-7
- ISSN
- 0179-7158 (ISSN-L)
- 1439-099X
- OpenAlex
- W1496148327
- Cited by
- 25
- References
- 40
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 2 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Strahlentherapie und Onkologie (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- radiotherapy efficacy, erythropoietin receptor, squamous cell carcinoma, A431 cells, tumor xenografts, hypoxia-inducible factor-1α, tumor vasculature, apoptosis, clonogenicity, tumor hypoxia
- MeSH terms
- Animals, Carcinoma, Squamous Cell, Cell Division, Erythropoietin, Female, Humans, Neoplasm Transplantation, Radiation-Sensitizing Agents, Recombinant Proteins, Soft Tissue Neoplasms, Transplantation, Heterologous, Tumor Stem Cell Assay, Mice, SCID, Apoptosis, Cell Line, Tumor, Mice, In Vitro Techniques
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