title: Erythropoietin/erythropoietin-receptor system as an angiogenic factor in chemically induced murine hepatic tumors.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiology, Kinki University School of Medicine, 77-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. kiyoshi@med.kindai.ac.jp
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nakamatsu
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kanamori
authors.forename: Osamu
authors.initials: O
authors.lastname: Maenishi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D002196:Capillaries / Q000737:chemistry; D004921:Erythropoietin / Q000032:analysis / Q000502:physiology*; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000098:blood supply* / Q000139:chemically induced / Q000737:chemistry; D008297:Male; D008749:Methyldimethylaminoazobenzene; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D017467:Receptors, Erythropoietin / Q000032:analysis / Q000502:physiology*
chemical_list: D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D008749:Methyldimethylaminoazobenzene