Integrin alphavbeta6 mediates HT29-D4 cell adhesion to MMP-processed fibrinogen in the presence of Mn2+.
Mn(2+) was found to induce adhesion of HT29-D4 adenoma carcinoma cells to fibrinogen (Fb). This was independent of the expression of the beta3 integrin subunit and involved endogenous alphavbeta6 but not alphavbeta5 integrin. Thus, addition of Mn(2+) led to a change in integrin alphavbeta6 specificity. Furthermore, Mn(2+) was found to strongly activate the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway in the HT29-D4 cell line. As a MAPK inhibitor strongly reduced the Mn(2+)-induced cell adhesion to Fb, it is suggested that a link between MAPK activation and cell adhesion to Fb exists. Both expression and activity of matrix metalloproteinase-9 (MMP-9) were enhanced by Mn(2+) and this led to Fb processing. MMP inhibitors prevented Mn(2+)-mediated cell adhesion to Fb, leading us to suggest that Mn(2+) promoted convergent changes in integrin alphavbeta6 conformation and Fb structure through activation of ERK/MAPK and MMP-9. Finally, we found that Mn(2+) and activators of the ERK pathway cooperated in HT29-D4 cell adhesion to Fb. Such a process may be involved in bone metastasis of some cancer cells.
Fouchier
Francis
F
Laboratoire de Génie Génétique et Biotechnologie, INSERM 476, INRA 1260, Faculté de Pharmacie, 27 Bd Jean Moulin, F-13385 Marseille cedex 5, France.
Penel
Claude
C
Pierre Montero
Marie
M
Bremond
Patricia
P
Champion
Serge
S
D000951:Antigens, Neoplasm / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D019030:Receptors, Vitronectin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D019096:Vitronectin / Q000378:metabolism
D000951:Antigens, Neoplasm; D005353:Fibronectins; D006133:Growth Substances; D039302:Integrin alphaVbeta3; D016023:Integrins; D009842:Oligopeptides; D019030:Receptors, Vitronectin; D019096:Vitronectin; C064660:integrin alphaVbeta5; C073878:integrin alphavbeta6; D008345:Manganese; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9; D008274:Magnesium; D013755:Tetradecanoylphorbol Acetate