Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma.
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.
Rasi
Guido
G
National Research Council, Istituto di Neurobiologia e Medicina Molecolare, Via Fosso del Cavaliere 100, 00133 Rome, Italy.
Serafino
Annalucia
A
Bellis
Lia
L
Lonardo
Maria Teresa
MT
Andreola
Federica
F
Zonfrillo
Manuela
M
Vennarecci
Giovanni
G
Pierimarchi
Pasquale
P
Sinibaldi Vallebona
Paola
P
Ettorre
Giuseppe Maria
GM
Santoro
Eugenio
E
Puoti
Claudio
C
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
D015415:Biomarkers; D020932:Nerve Growth Factor; D020917:Receptor, trkA