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Erythropoietin/erythropoietin‐receptor system is involved in angiogenesis in human hepatocellular carcinoma
Author(s) -
Ribatti D,
Marzullo A,
Gentile A,
Longo V,
Nico B,
Vacca A,
Dammacco F
Publication year - 2007
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2007.02654.x
Subject(s) - erythropoietin receptor , angiogenesis , erythropoietin , hepatocellular carcinoma , cd31 , cancer research , medicine , vascular endothelial growth factor , paracrine signalling , receptor , pathology , biology , vegf receptors
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.