| Betanectin (BN) is a secretory protein responsive to upregulation by Transforming Growth Factor beta1 (TGFbeta1). BN is a member of the Fasciclin I (Fas I) family of cell surface molecules, all of which function in cell to cell and cell to extracellular matrix (ECM) binding. The association of BN with the cell surface is by members of the integrin family of receptors. Recently, BN has been suggested to influence the balance between cell survival and cell death of various cell types through activation of integrins. This study demonstrates BN induced apoptosis of MG-63 osteosarcoma cells in response to TGFbeta1, and when recombinant BN is used as a supplement in cell-growth medium. The apoptotic signal of BN was confined to its C-terminus, which was found to be susceptible to C-terminal processing, and BN-mediated apoptosis was reduced as a result of downregulation of integrins alpha3beta1 and alpha4beta1. During embryonic development, BN protein expression was localized to areas that express TGFbeta1 and that had a high incidence of apoptosis. These results suggest that BN-mediated apoptosis is an underlying response to TGFbeta1 pluripotent actions in biological processes that include tumor suppression, tissue development and morphogenesis, and angiogenesis. |
