Integrin alpha v beta 3 promotes anchorage-dependent apoptosis in human intestinal carcinoma cells

A population of cells surviving during prolonged incubation in suspension ( anoikis-negative cells) were selected from the original anoikis-positive hu man intestinal carcinoma cell line Caco-2. Anoikis-negative cells are chara cterized by a strong transcriptional downregulation of the alphav-integrin chain as detected by FACS analysis, RT-PCR and Northern blotting. This find ing suggested that ow-integrin generates a signal stimulating apoptosis of Caco-2 cells upon their detachment from the extracellular matrix. Two lines of evidence supporting this suggestion were provided. First, activation of the alphav beta3 integrin on Caco-2 cells by their treatment with an alpha v beta3-specific monoclonal antibody resulted in marked stimulation of anoi kis. Second, treatment of Caco-2 cells with alphav-specific antisense oligo nucleotide resulted in downregulation of the expression of alphav chain and in elevated resistance of these cells to anoikis. Thus, for the first time , our data prove that alphav beta3 integrin can be an active transducer of apoptosis-stimulating signals generated in response to disruption of the ce ll-matrix contacts.