Epo is involved in angiogenesis in human glioma |
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Authors: | Beatrice Nico Tiziana Annese Diego Guidolin Nicoletta Finato Enrico Crivellato Domenico Ribatti |
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Affiliation: | (1) Department of Human Anatomy and Histology, University of Bari Medical School, Piazza Giulio Cesare, 11, Policlinico, 70124 Bari, Italy;(2) Section of Anatomy, Department of Human Anatomy and Physiology, University of Padua Medical School, Padua, Italy;(3) Section of Pathology, Department of Medical and Morphological Research, University of Udine Medical School, Udine, Italy;(4) Section of Anatomy, Department of Medical and Morphological Research, University of Udine Medical School, Udine, Italy; |
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Abstract: | In this study, the extent of angiogenesis, evaluated as microvascular density, and the immunoreactivity of tumor cells to erythropoietin (Epo) and of endothelial cells to Epo receptor (EpoR) have been correlated in human glioma specimens, and the effect of anti-Epo antibody on glioma-induced angiogenesis in vivo in the chick embryo chorioallantoic membrane (CAM) has been investigated. Results show that: (1) Epo/EpoR expression correlates with angiogenesis, (2) in the CAM assay, tumor bioptic specimens induce a strong angiogenic response, comparable to that induced by VEGF, and (3) an anti-Epo antibody co-administered with tumor bioptic specimens significantly inhibits the angiogenic response. These findings suggest the presence of a loop in the Epo/EpoR system, i.e. Epo is secreted by glioma tumor cells and it affects glioma vascular endothelial cells via its receptor and promotes angiogenesis in a paracrine manner. Moreover, as demonstrated by in vivo experiments, Epo is responsible for the strong angiogenic response induced by human glioma bioptic specimens, because an anti-Epo antibody is able to significantly inhibit this response. |
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