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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-11-18
pubmed:abstractText
Liver carcinogenesis is associated with striking changes in the integrin repertoire of hepatocytes, including the overexpression of the laminin and collagen receptors alpha1beta1 and the de novo induction of the laminin receptor alpha6beta1. Our aim was to analyze the role of pro-inflammatory cytokines, interferons and fibrogenic cytokines TGF-beta and FGF2 in the regulation of the expression of beta1 integrins by neoplastic hepatocytes. The 2 human hepatocellular cell lines HepG2 and Hep3B were used as models. Integrin expression was assessed by qualitative methods (immunocytochemistry, Western blotting) and semi-quantitative techniques (FACS, cellular ELISA), before and after stimulation by TNFalpha, IL1-beta, TGF-beta, FGF2, interferon gamma and interferon alpha-2b. HepG2 and Hep3B constitutively expressed alpha1, alpha2, alpha6 and beta1 chains. A 24 to 48-hr stimulation with pro-inflammatory cytokines, TGF-beta and FGF2 induced a significant increase in the concentrations of all integrin chains. The maximum induction was registered for beta1 chain, which presented increases amounting up to 3, 4 and 7 times the control values in the presence of, respectively, TNF alpha/IL1-beta, TGF-beta and FGF2. Interferons had no direct effect on integrin expression and partially antagonized the effects of TNF alpha and TGF-beta. The increased concentrations of integrin chains were associated with an increased membrane expression of the corresponding dimers and with an increased adhesion of stimulated hepatocytes to laminin, which was antagonized by neutralizing anti-beta1 and anti-alpha6 antibodies. Finally, anti-alpha6 antibody inhibited the migration of HepG2 and Hep3B cells in reconstituted basement membrane. Our results suggest that the stimulation of alpha6beta1 integrin expression in hepatocarcinoma cells is essential for cell adhesion and migration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
518-25
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10508489-Carcinoma, Hepatocellular, pubmed-meshheading:10508489-Cell Adhesion, pubmed-meshheading:10508489-Cell Membrane, pubmed-meshheading:10508489-Cell Movement, pubmed-meshheading:10508489-Dose-Response Relationship, Drug, pubmed-meshheading:10508489-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:10508489-Fibroblast Growth Factor 2, pubmed-meshheading:10508489-Flow Cytometry, pubmed-meshheading:10508489-Humans, pubmed-meshheading:10508489-Immunoblotting, pubmed-meshheading:10508489-Immunohistochemistry, pubmed-meshheading:10508489-Integrin alpha6beta1, pubmed-meshheading:10508489-Integrins, pubmed-meshheading:10508489-Interferon-alpha, pubmed-meshheading:10508489-Interferon-gamma, pubmed-meshheading:10508489-Interleukin-1, pubmed-meshheading:10508489-Liver Neoplasms, pubmed-meshheading:10508489-Recombinant Proteins, pubmed-meshheading:10508489-Transforming Growth Factor beta, pubmed-meshheading:10508489-Tumor Cells, Cultured, pubmed-meshheading:10508489-Tumor Necrosis Factor-alpha
pubmed:year
1999
pubmed:articleTitle
alpha6beta1 integrin expression in hepatocarcinoma cells: regulation and role in cell adhesion and migration.
pubmed:affiliation
Laboratoire de Biologie Cellulaire, Unité INSERM U327, Faculté de Médecine Xavier Bichat, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't