Expression of somatostatin receptors in normal and cirrhotic human liver and in hepatocellular carcinoma
- H Reynaert1,*,
- K Rombouts2,*,
- A Vandermonde3,
- D Urbain4,
- U Kumar5,
- P Bioulac-Sage6,
- M Pinzani7,
- J Rosenbaum8,
- A Geerts3
- 1Laboratory for Molecular Liver Cell Biology, Free University of Brussels (VUB), and Division of Gastroenterology-Hepatology, University Hospital, Free University of Brussels (VUB), Brussels, Belgium
- 2Laboratory for Molecular Liver Cell Biology, Free University of Brussels (VUB),, Brussels, Belgium, and Dipartimento di Medicina Interna, Università degli Studi di Firenze, Firenze, Italy
- 3Laboratory for Molecular Liver Cell Biology, Free University of Brussels (VUB), Brussels, Belgium
- 4Division of Gastroenterology-Hepatology, University Hospital, Free University of Brussels (VUB), Brussels, Belgium
- 5Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Canada
- 6Groupe de Recherche pour l’ Etude du Foie, INSERM E0362 and IFR 66, Université Victor Segalen, Bordeaux 2, France, and Pathology Department, University Hospital, Bordeaux, France
- 7Dipartimento di Medicina Interna, Università degli Studi di Firenze, Firenze, Italy
- 8Groupe de Recherche pour l’ Etude du Foie, INSERM E0362 and IFR 66, Université Victor Segalen, Bordeaux 2, France
- Correspondence to:
Dr H Reynaert
Department of Gastroenterology-Hepatology, University Hospital Vrije Universiteit Brussel (AZ-VUB), Laarbeeklaan 101,B-1090 Brussels, Belgium;
- Accepted 1 February 2004
Background: Somatostatin analogues have been used with conflicting results to treat advanced hepatocellular carcinoma (HCC). The aim of this study was to investigate expression of somatostatin receptor (SSTR) subtypes in human liver, and to examine the effect of selective SSTR agonists on proliferation, apoptosis, and migration of hepatoma cells (HepG2, HuH7) and hepatic stellate cells (HSCs).
Methods: Expression of SSTRs in cell lines, normal and cirrhotic liver, and HCC was examined by immunohistochemistry and reverse transcription-polymerase chain reaction. Effects of SSTR agonists on proliferation and apoptosis of tumour cells and HSCs were assessed by the 5-bromo-2′ deoxyuridine and TUNEL methods, respectively. The influence of SSTR agonists on migration was investigated using Boyden chambers.
Results: In normal liver, both hepatocytes and HSCs were negative for all five SSTRs. Cirrhotic liver and HCC as well as cultured hepatoma cells and HSCs expressed all five SSTRs, both at the protein and mRNA levels, except for HuH7 cells which did not immunoreact with SSTR3. None of the agonists influenced proliferation or apoptosis. However, compared with untreated cells, L-797,591, an SSTR1 agonist, reduced migration of HepG2, HuH7, and HSCs significantly to 88 (7)% (p<0.05), 83 (11)% (p<0.05), and 67 (13)% (p<0.01), respectively.
Conclusions: Cirrhotic liver and HCC express SSTRs. Although the somatostatin analogues used in this study did not affect proliferation and apoptosis, stimulation of SSTR1 may decrease invasiveness of HCC by reducing migration of hepatoma cells and/or HSCs. Clinical trials evaluating somatostatin analogues for the treatment of HCC should take these findings into account.
- α-SMA, α smooth muscle actin
- BrdU, 5- bromo-2′ deoxyuridine
- DMEM, Dulbecco’s modified Eagle’s medium
- HCC, hepatocellular carcinoma
- HGF, hepatocyte growth factor
- HSCs, hepatic stellate cells
- PDGF, platelet derived growth factor
- PDGFR-β, platelet derived growth factor receptor β
- RT-PCR, reverse transcription-polymerase chain reaction
- SSTR, somatostatin receptor
↵* H Reynaert and K Rombouts contributed equally to this study.