title: Darbepoetin-α Promotes Cell Proliferation in Established Extrahepatic Colorectal Tumors after Major Hepatectomy.
abstract: BACKGROUND
  The glycoprotein hormone erythropoietin and its analogue darbepoetin-α (DPO) have been shown to reduce the risk of acute liver failure after major hepatectomy. However, previous experimental studies have also shown that DPO significantly enhances neovascularization and tumor cell proliferation in established colorectal liver metastasis in hepatectomized and nonhepatectomized mice. The present study now analyzes whether DPO influences cell proliferation and migration as well as vascularization and growth of established colorectal metastasis at extrahepatic sites after major hepatectomy.
  
  
  METHODS
  GFP-transfected CT26.WT colorectal cancer cells were implanted into dorsal skinfold chambers of syngeneic BALB/c mice. Five days after tumor cell implantation, the animals received a single dose of DPO (10 µg/kg body weight) or phosphate-buffered saline solution (PBS) intravenously. Additional animals received a 70% hepatectomy and DPO or PBS treatment. Tumor vascularization and growth as well as tumor cell migration, proliferation and apoptosis were studied repetitively over 14 days using intravital fluorescence microscopy, histology and immunohistochemistry.
  
  
  RESULTS
  DPO did not influence tumor cell migration and apoptosis. In addition, DPO did not stimulate tumor cell infiltration or vascularization; however, significantly increased tumor cell proliferation was detected in hepatectomized animals.
  
  
  CONCLUSIONS
  DPO increases cell proliferation in established extrahepatic colorectal metastases after major hepatectomy. Thus, DPO may not be recommended to stimulate regeneration of the remnant liver after major hepatectomy for colorectal liver metastasis.
authors.affiliation: Institute for Clinical and Experimental Surgery, Homburg/Saar, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Senger
authors.forename: Otto
authors.initials: O
authors.lastname: Kollmar
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Kathrin
authors.initials: K
authors.lastname: Rupertus
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000473:pathology / Q000601:surgery*; D000068256:Darbepoetin alfa / Q000494:pharmacology*; D005260:Female; D006498:Hepatectomy; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000628:therapy
chemical_list: D000068256:Darbepoetin alfa