Alpha integrin subunits regulate human (Caco-2) intestinal epithelial proliferation and phenotype

Background/Aims: Cell-matrix interactions influence intestinal epithelial biology, but the whether specific integrin heterodimers exert different effects is unclear. Methods: We used functional antibodies to investigate effects of the alpha 2, alpha 3, alpha 5, and alpha 6 integrin subunits on proliferation and differentiation of human intestinal Caco-2 cells on laminin. Cells seeded onto laminin-coated inserts in defibronectinized medium were treated with functional antibodies or normal IgG for 72 hrs and proliferation, alkaline phosphatase and dipeptidyl dipeptidase specific activity were measured. Results: Caco-2 adhesion to antibody to each alpha-integrin subunit stimulated tyrosine phosphorylation of Focal Adhesion Kinase and paxillin, suggesting that these antibodies intiate integrin-related tyrosine signalling. Proliferation was inhibited by anti-alpha 2 and anti- alpha 3, but stimulated by anti- alpha 6. Alkaline phosphatase and dipeptidyl dipeptidase specific activity were promoted by alpha 2 blockade but decreased after alpha 6 blockade. Proliferative blockade using mitomycin C or hydroxyurea prevented the effects of alpha 2 ligation on differentiation, but the decrease in alkaline phosphatase specific activity observed after alpha 6 integrin subunit blockade was preserved even after proliferative blockade. Conclusion: Integrin heterodimers modulate human Caco-2 intestinal epithelial biology on laminin in an alpha-subunit specific manner. The different effects of anti-alpha 2 and anti- alpha 6 may reflect competitition by these antibodies with integrin subunit interactions with laminin as well as initiation of their own signals or different functions for the alpha 6 integrin subunit. Copyright (C) 2000 S. Karger AG, Basel.