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Erythropoietin/erythropoietin-receptor system is involved in angiogenesis in human hepatocellular carcinoma
Article first published online: 26 MAR 2007
Volume 50, Issue 5, pages 591–596, April 2007
How to Cite
Ribatti, D., Marzullo, A., Gentile, A., Longo, V., Nico, B., Vacca, A. and Dammacco, F. (2007), Erythropoietin/erythropoietin-receptor system is involved in angiogenesis in human hepatocellular carcinoma. Histopathology, 50: 591–596. doi: 10.1111/j.1365-2559.2007.02654.x
- Issue published online: 26 MAR 2007
- Article first published online: 26 MAR 2007
- Date of submission 16 August 2006 Accepted for publication 25 August 2006
- erythropoietin receptor;
- hepatocellular carcinoma
Aims: To correlate microvascular density and erythropoietin (Epo)/Epo-receptor (EpoR) expression in endothelial and tumour cells with histopathological type in hepatocellular carcinoma (HCC).
Methods and results: Specimens of primary HCC obtained from 50 patients who had undergone curative hepatectomy were investigated immunohistochemically by using anti-CD31, anti-Epo and anti-EpoR antibodies. Poorly differentiated HCC had a higher degree of vascularization than other stages and Epo/EpoR expression in both tumour and endothelial cells increased in parallel with grade of malignancy and was highly correlated with the extent of angiogenesis.
Conclusions: Epo/EpoR levels correlate with angiogenesis and progression of patients with HCC and these findings suggest the presence of a loop in the Epo/EpoR system, i.e. Epo is secreted by hepatic tumour cells and it affects vascular endothelial cells via its receptors and promotes angiogenesis in a paracrine manner. It is thus suggested that Epo is an important factor in hepatic tumour angiogenesis. Understanding the mechanisms of HCC angiogenesis provides a basis for a rational approach to the development of antiangiogenic therapy in patients with hepatic cancer.