Integrin αvβ6 mediates HT29-D4 cell adhesion to MMP-processed fibrinogen in the presence of Mn2+

Mn2+ was found to induce adhesion of HT29-D4 adenoma carcinoma cells to fibrinogen (Fb). This was independent of the expression of the β3 integrin subunit and involved endogenous αvβ6 but not αvβ5 integrin. Thus, addition of Mn2+ led to a change in integrin αvβ6 specificity. Furthermore, Mn2+ 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 Mn2+-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 Mn2+ and this led to Fb processing. MMP inhibitors prevented Mn2+-mediated cell adhesion to Fb, leading us to suggest that Mn2+ promoted convergent changes in integrin αvβ6 conformation and Fb structure through activation of ERK/MAPK and MMP-9. Finally, we found that Mn2+ 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.