Abstract

Background: Integrins mediate cell matrix adhesion and regulate cell growth and survival. In colonic epithelial cells, α₂β₁ integrin controls glandular differentiation and proliferation. Butyrate stimulates differentiation and induces apoptosis in vitro.

Aims: We investigated whether butyrate induction of apoptosis was associated with perturbation of integrin mediated cell matrix adhesion.

Methods: Three colonic cancer cell lines (SW1222, SW620, LS174T) were studied. Adhesion to extracellular matrix proteins, expression of α₂β₁ integrin, and apoptosis were studied in adherent cells after treatment with 4 mM butyrate.

Results: Butyrate decreased the attachment to type I collagen in SW620 cells and type I and IV collagen in LS174T cells. The decreased cell attachment was associated with downregulation of α₂β₁ integrin and increased apoptosis in adherent cells. No changes in α₂β₁ expression or matrix adhesion were seen in SW1222 cells, which were also found to be less sensitive to butyrate induction of apoptosis. Downregulation of α₂β₁ integrin preceded the detection of apoptosis.

Conclusion: Apoptosis induced by butyrate is associated with downregulation of expression and functional activity of α₂β₁ integrin. Perturbation of cell matrix adhesion may be a novel mechanism by which butyrate induces apoptosis in colorectal cancer cells.