Abstract
Ribatti D, Poliani P L, Longo V, Mangieri D, Nico B & Vacca A (2007) Histopathology50, 636–641 Erythropoietin/erythropoietin receptor system is involved in angiogenesis in human neuroblastomaAimsPrevious studies have shown that increased vascularity is associated with tumour progression in human neuroblastoma (NB). The involvement of erythropoietin (Epo) in tumour angiogenesis has also been reported. The aim of this study was to correlate microvascular density and Epo/Epo-receptor (EpoR) expression in endothelial and tumour cells to the clinical stage of NB.Methods and resultsSpecimens of NB obtained from 20 patients were investigated immunohistochemically by using anti-CD31, anti-Epo and anti-EpoR antibodies. The extent of angiogenesis was found to be up-regulated in advanced disease. In keeping with this observation, Epo/EpoR expression in tumour and endothelial cells, respectively, was also highly correlated with the extent of angiogenesis and higher clinical stage.ConclusionsThe correlation of Epo/EpoR expression with angiogenesis and tumour progression suggests the presence of a loop in the Epo–EpoR system. Epo is secreted by tumour cells and affects vascular endothelial cells via its receptor, promoting tumour angiogenesis in a paracrine manner. Data suggest that Epo represents an important mediator in NB angiogenesis. Understanding the mechanisms of NB angiogenesis provides the basis for a rational approach to the development of antiangiogenic therapy in patients affected by NB.
Highlights
Neuroblastoma (NB) is the most common malignant tumour in infants and the fourth most common in children > 1 year old.[1]
Our data demonstrate that the extent of angiogenesis in human NB, evaluated as microvessel density, increases progressively along with clinical stage
Different molecules and angiogenic factors are involved in tumour angiogenesis in human NB
Summary
Neuroblastoma (NB) is the most common malignant tumour in infants and the fourth most common in children > 1 year old.[1] Angiogenesis, i.e. the formation of new blood vessels from pre-existing ones, is important in carcinogenesis as well as in the tumour progression of human solid and haematological tumours.[2,3] NB, in particular, shows wide histological variability that reflects different steps in tumour maturation and angiogenesis appears to play an important role in determining tumour phenotype.[4] Many angiogenic stimulators, such as vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), as well as inhibitors, such as tissue inhibitors of matrix. Epo–EpoR and angiogenesis in human neuroblastoma 637 metalloproteinases (MMPs), have been detected in neuroblastic tumours.[5,6,7] High tumour vascularity correlates with metastatic disease, myc amplification, unfavourable biology and poor outcome; by contrast, low tumour vascularity is associated with favourable prognostic features, such as localized disease and favourable histology.[8,9,10,11]
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