Rasi G, Serafino A, Bellis L, Lonardo MT, Andreola F, Zonfrillo M, Vennarecci G, Pierimarchi P, Vallebona PS, Ettorre GM, Santoro E, Puoti C. Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma. World J Gastroenterol 2007; 13(37): 4986-4995 [PMID: 17854142 DOI: 10.3748/wjg.v13.i37.4986]
Corresponding Author of This Article
Dr. Annalucia Serafino, National Research Council, Istituto di Neurobiologia e Medicina Molecolare, Via Fosso del Cavaliere 100, 00133, Rome, Italy. annalucia.serafino@artov.inmm.cnr.it
Article-Type of This Article
Liver Cancer
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World J Gastroenterol. Oct 7, 2007; 13(37): 4986-4995 Published online Oct 7, 2007. doi: 10.3748/wjg.v13.i37.4986
Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma
Guido Rasi, Annalucia Serafino, Lia Bellis, Maria Teresa Lonardo, Federica Andreola, Manuela Zonfrillo, Giovanni Vennarecci, Pasquale Pierimarchi, Paola Sinibaldi Vallebona, Giuseppe Maria Ettorre, Eugenio Santoro, Claudio Puoti
Guido Rasi, Annalucia Serafino, Federica Andreola, Manuela Zonfrillo, Pasquale Pierimarchi, Institute of Neurobiology and Molecular Medicine, National Research Council, 00185 Rome, Italy
Lia Bellis, Hepatic Haemodynamic Unit, Marino Hospital, 00185 Rome, Italy
Maria Teresa Lonardo, Giovanni Vennarecci, Giuseppe Maria Ettorre, Eugenio Santoro, Division of Surgical Oncology and Liver Transplantation, Regina Elena Cancer Institute, 00185 Rome, Italy
Paola Sinibaldi Vallebona, Department of Experimental Medicine and Biochemical Science, University of Rome “Tor Vergata”, 00185 Rome, Italy
Claudio Puoti, Department of Internal Medicine and Digestive Diseases, Marino Hospital, Rome, Italy
Author contributions: All authors contributed equally to the work.
Supported by Grant N° RF 01.115 from Ministero della Salute, Ricerca Finalizzata
Correspondence to: Dr. Annalucia Serafino, National Research Council, Istituto di Neurobiologia e Medicina Molecolare, Via Fosso del Cavaliere 100, 00133, Rome, Italy. annalucia.serafino@artov.inmm.cnr.it
Telephone: +39-6-49934202 Fax: +39-6-49934257
Received: May 16, 2007 Revised: July 2, 2007 Accepted: July 26, 2007 Published online: October 7, 2007
Abstract
AIM: To define NGF (nerve growth factor) and its high-affinity receptor trkANGF 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 trkANGF 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 trkANGF 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 trkANGF were negative. NGF serum levels in cirrhotic and/or HCC patient were up to 25-fold higher than in controls.
CONCLUSION: 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.
