title: Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma.
abstract: OBJECTIVE
  To define NGF (nerve growth factor) and its high-affinity receptor trkA(NGF) presence and distribution in fibrotic liver and in HCC, and to verify if NGF might have a role in fibrosis and HCC.
  
  
  METHODS
  Intracellular distribution of NGF and trkA(NGF) were assessed by immunohistochemistry and immuno-electron microscopy in liver specimens from HCC, cirrhosis or both. ELISA was used to measure circulating NGF levels.
  
  
  RESULTS
  NGF and trkA(NGF) were highly expressed in HCC tissue, mainly localized in hepatocytes, endothelial and some Kupffer cells. In the cirrhotic part of the liver they were also markedly expressed in bile ducts epithelial and spindle-shaped cells. Surprisingly, in cirrhotic tissue from patients without HCC, both NGF and trkA(NGF) were negative. NGF serum levels in cirrhotic and/or HCC patient were up to 25-fold higher than in controls.
  
  
  CONCLUSIONS
  NGF was only detected in liver tissue with HCC present. Intracellular distribution suggests paracrine and autocrine mechanisms of action. Better definition of mechanisms may allow for therapeutic and diagnostic/prognostic use of NGF.
authors.affiliation: National Research Council, Istituto di Neurobiologia e Medicina Molecolare, Via Fosso del Cavaliere 100, 00133 Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Rasi
authors.forename: Annalucia
authors.initials: A
authors.lastname: Serafino
authors.forename: Lia
authors.initials: L
authors.lastname: Bellis
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Lonardo
authors.forename: Federica
authors.initials: F
authors.lastname: Andreola
authors.forename: Manuela
authors.initials: M
authors.lastname: Zonfrillo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vennarecci
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pierimarchi
authors.forename: Paola
authors.initials: P
authors.lastname: Sinibaldi Vallebona
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Ettorre
authors.forename: Eugenio
authors.initials: E
authors.lastname: Santoro
authors.forename: Claudio
authors.initials: C
authors.lastname: Puoti
mesh_terms: D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D020932:Nerve Growth Factor / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism
chemical_list: D015415:Biomarkers; D020932:Nerve Growth Factor; D020917:Receptor, trkA