Department of Human Anatomy and Histology, University of Bari Medical School, Piazza Giulio Cesare, 11, Policlinico, 70124 Bari, Italy.
J Neurooncol. 2011 Mar;102(1):51-8. doi: 10.1007/s11060-010-0294-6. Epub 2010 Jul 9.
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.
在这项研究中,我们评估了人类脑胶质瘤标本中的血管生成程度(以微血管密度表示)和肿瘤细胞对促红细胞生成素(Epo)的免疫反应性以及内皮细胞对 Epo 受体(EpoR)的免疫反应性,并研究了抗 Epo 抗体对鸡胚尿囊膜(CAM)中脑胶质瘤诱导的血管生成的体内作用。结果表明:(1)Epo/EpoR 表达与血管生成相关;(2)在 CAM 测定中,肿瘤活检标本诱导强烈的血管生成反应,与 VEGF 诱导的反应相当;(3)与肿瘤活检标本共同给予的抗 Epo 抗体可显著抑制血管生成反应。这些发现表明 Epo/EpoR 系统中存在一个循环,即 Epo 由脑胶质瘤肿瘤细胞分泌,并通过其受体影响脑胶质瘤血管内皮细胞,以旁分泌方式促进血管生成。此外,如体内实验所示,Epo 是人类脑胶质瘤活检标本诱导的强烈血管生成反应的原因,因为抗 Epo 抗体能够显著抑制这种反应。