Fig. 3. Matrix status influences proteinase expression.

Left: Model for integrin-matrix interactions. The physical nature of the integrin-ligand interaction dictates the formation of specific signal transduction complexes on a cytoskeletal framework. (A, C) Low valency integrin occupancy can be induced by matrix protein fragments (A) or soluble integrin subunit-specific antibodies (C) and results in redistribution of the integrin to focal adhesions without activation of tyrosine kinase signaling or accumulation of cytoskeletal components. (B,D) Integrin occupancy by a multivalent ligand such as presented by intact extracellular matrix (B) leads to a more robust cytoplasmic response characterized by the accumulation of a large variety of cytoskeletal (e.g., talin, α-actinin, paxillin) and signaling (e.g., Src, ERK, JNK) molecules at the cytoplasmic face of the integrin. This response can be mimiced by integrin subunit-specific antibodies immobilized on beads (D). [adapted from Yamada, K. M. and Miyamoto, S. Curr Opin Cell Biol, 7: 681-689, 1995]

Right: Response of ovarian cancer cells to integrin engagement. upper panel: Cells in contact with a 2D collagen surface (‘thin deposit’ or ‘gelatin’) do not exhibit an altered proteinase response (appearance of active proteinase designated “MMP-2”); while cells cultured in 3D collagen gels (‘type I collagen’ or ‘type I CR collagen’) exhibit enhanced proMMP-2 activation (zymogram upper right) mediated via increased expression and activity of MT1-MMP (not shown). Lower panels. Use of integrin subunit-specific antibodies to mimic matrix status. Soluble antibodies ligate integrins (similar to 2D matrix) while bead-immobilized antibodes ligate and aggregate integrins. While soluble antibodies do not induce proMMP-2 activation (zymogram middle), cells respond to bead-immobilized α3- or β1-antibodies by enhanced proMMP-2 activation (zymogram lower right) mediated via increased expression and activity of MT1-MMP (not shown).