Hepatocarcinoma cell lines down-regulate matrix metalloproteinase-2 expression in human hepatic myofibroblasts.
Matrix metalloproteinases (MMPs) are a family of proteases that degrade extracellular matrix components and are involved in tumor progression and metastasis. We studied the pattern of expression of MMP-2 by human hepatoma cell lines and human hepatic myofibroblasts and its regulation in co-culture between these cell types. MMP-2 expression was studied by zymography and semi-quantitative RT-PCR. The expression of MT1-MMP (involved in MMP-2 activation) was studied by Western blot analysis and RT-PCR and the secretion of TIMP-2 by ELISA and RT-PCR. Myofibroblasts expressed high levels of MMP-2, MT1-MMP and TIMP-2. The hepatoma cell lines HepG2, HuH7 and Hep3B did not express MMP-2 and weakly expressed TIMP-2 and MT1-MMP. In co-culture, no modulation of MT1-MMP or TIMP-2 expression was observed. A strong decrease in myofibroblast MMP-2 expression was seen in the presence of hepatoma cell lines. This was partly reproduced by their conditioned media. We conclude that hepatoma cell lines down-regulate the expression of MMP-2 by myofibroblasts.
Blanc
Jean-Frédéric
JF
Laboratoire de Biologie des Tumeurs et du Développement, INSERM E9917, Université Victor Segalen, Bordeaux 2, 146 rue Léo Saignat, 33076, France. jean-frederic.blanc@chu-bordeaux.fr
Bisson
Christèle
C
Frankenne
Francis
F
Noël
Agnès
A
Munaut
Carine
C
Colige
Alain
A
Collette
Julien
J
Rosenbaum
Jean
J
Foidart
Jean-Michel
JM
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D015536:Down-Regulation; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008099:Liver / Q000201:enzymology*; D008113:Liver Neoplasms / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D007334:Insulin-Like Growth Factor I; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2