Erythropoietin/erythropoietin-receptor system as an angiogenic factor in chemically induced murine hepatic tumors.

Background: To clarify the role of erythropoietin (Epo) in hepatic tumor angiogenesis, expression of Epo and its receptor (Epo-R) and content of Epo were investigated in murine chemically induced hepatic tumors.

Methods: To induce hepatic tumors and cirrhosis, diaminobenzidine was administered to Wistar rats for 5 months. In total, 30 hepatic tumors of greater than 3 mm in diameter were induced in 12 rats. The 30 hepatic tumors were resected with the surrounding hepatic tissues. The Epo content was measured by a radioimmunoassay (RIA) method. The number of tumor vessels in a definite area was counted in 100 areas of each tumor. To demonstrate the expression of Epo-R in tumors or surrounding liver tissues, immunohistochemical staining for Epo-R was performed.

Results: The Epo content of tumors ranged from 6.1 to 97.8 mU/ml, with a median of 21.8 mU/ml, which was significantly higher than that of the cirrhotic tissues adjacent to the tumors. Epo was not detectable in the normal or cirrhotic liver tissues without tumors. A significant correlation between Epo content and vascular density was noted in the 30 hepatic tumors (correlation coefficient, 0.480; P = 0.01). Immunoreactive Epo-R was detectable in the endothelium of intervening vessels of all hepatic tumors examined.

Conclusion: The Epo/Epo-R system is related to the angiogenesis of murine hepatic tumors. To clarify the role of erythropoietin (Epo) in hepatic tumor angiogenesis, expression of Epo and its receptor (Epo-R) and content of Epo were investigated in murine chemically induced hepatic tumors.