Role of myofibroblasts in tumour encapsulation of hepatocellular carcinoma in haemochromatosis

Bridle, Kim R., Crawford, Darrell H. G., Powell, Lawrie W. and Ramm, Grant A. (2001) Role of myofibroblasts in tumour encapsulation of hepatocellular carcinoma in haemochromatosis. Liver, 21 2: 96-104. doi:10.1034/j.1600-0676.2001.021002096.x

Author Bridle, Kim R.
Crawford, Darrell H. G.
Powell, Lawrie W.
Ramm, Grant A.
Title Role of myofibroblasts in tumour encapsulation of hepatocellular carcinoma in haemochromatosis
Journal name Liver   Check publisher's open access policy
ISSN 0106-9543
Publication date 2001-04
Sub-type Article (original research)
DOI 10.1034/j.1600-0676.2001.021002096.x
Volume 21
Issue 2
Start page 96
End page 104
Total pages 9
Editor Alaistair Burt
Place of publication Denmard
Publisher Blackwell Munksgaard
Collection year 2001
Language eng
Subject C1
321006 Gastroenterology and Hepatology
730113 Digestive system and disorders
Abstract Background/Aims: Hepatocellular carcinoma is a carcinoma malignancy and a major complication of untreated haemochromatosis. Encapsulation of liver tumours has been associated with a better prognosis and longer disease-free periods following resection, This study investigated the source of the tumour capsule in patients with haemochromatosis and coexisting hepatocellular carcinoma and examined potential factors influencing development. Methods: Five haemochromatosis patients with encapsulated hepatocellular carcinoma were studied. Myofibroblasts were identified using combined immunohistochemistry and in situ hybridisation for a-smooth muscle actin and procollagen alpha (1)(I) mRNA, respectively. Immunohistochemistry was also performed for transforming growth factor (TGF)-beta (1), platelet-derived growth factor (PDGF)-beta receptor and malondialdehyde. Results. Procollagen alpha (1)(I) mRNA co-localised to alpha -smooth muscle actin positive myofibroblasts. The number of myofibroblasts was maximal within the capsule and decreased away from the tumour. TGF-beta (1) protein was expressed in iron-loaded cells in non-tumour liver at the interface of tumour capsule. PDGF-beta receptor expression was observed in mesenchymal cells in the tumour capsule and in portal tracts. Malondialdehyde adducts were observed in the tumour, non-tumour tissue and in the capsule. Conclusions: This study provides evidence that myofibroblasts are the cell type responsible for collagen production within the tumour capsule surrounding hepatocellular carcinoma in haemochromatosis, The production of TGF-beta (1) by iron-loaded hepatic cells at the tumour capsule interface may perpetuate the myofibroblastic phenotype, resulting in, the formation of the tumour capsule.
Keyword Gastroenterology & Hepatology
Alpha-smooth Muscle Actin
Pdgf-beta Receptor
Hepatic Stellate Cells
Hepatocellular Carcinoma
Growth-factor Receptor
Genetic Hemochromatosis
Tissue Inhibitor
Oxidative Stress
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 16 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 14 Aug 2007, 16:04:14 EST