Epo is involved in angiogenesis in human glioma.
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.
Nico
Beatrice
B
Department of Human Anatomy and Histology, University of Bari Medical School, Piazza Giulio Cesare, 11, Policlinico, 70124 Bari, Italy.
Annese
Tiziana
T
Guidolin
Diego
D
Finato
Nicoletta
N
Crivellato
Enrico
E
Ribatti
Domenico
D
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism / Q000473:pathology; D004921:Erythropoietin / Q000378:metabolism*; D005910:Glioma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D012189:Retrospective Studies
D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D017467:Receptors, Erythropoietin; D004921:Erythropoietin