Structures involved in focal ECM degradation has been identified on several types of cells.
33 These structures, commonly referred to as podosomes or invadopodia, are specialized cell adhesion sites that are also involved in ECM degradation. They are central to macrophage ECM degradation, osteoclast bone resorption, metastatic cell invasion, diapedesis, cell motility, and migration.
34 35 36 37 38 39 40 Similar structures have been observed under some conditions in fibroblasts, endothelial cells, smooth muscle cells, and epithelial cells.
37 38 The size, shape, and molecular organization of these structures in various cell types are relatively diverse.
36 37 38 41 Simple podosomes, as are commonly found on the ventral surface of macrophages, are approximately 500 nm in diameter, with a vertical F-actin core and numerous actin-binding proteins and are surrounded by a ring of talin, paxillin, and vinculin.
37 38 Their formation is thought to be associated with cortactin clustering at discrete microdomains on the ventral surface of cells, perhaps recruited directly or indirectly by cdc42 and sometimes near sites where stress fibers insert into adhesion plaques or focal adhesions. N-WASP (neural-Wiscott-Aldrich syndrome protein) and Arp 2/3 (actin-related protein) are involved in branching of F-actin microfilaments and play important roles in podosome or invadopodia formation.
42 43 Invadopodia have longer lives and may evolve from simple podosomes,
36 which normally last only minutes to an hour. In some types of cells, 5-μm circular rosettes and larger complex aggregates or clusters of podosomes with less uniform structures are observed.
36 37 38 41 Components common to PILS include: cortactin, α-actinin, caldesmon, gelsolin, dynamin, F-actin, ARP 2/3, N-WASP, MMP-2, MMP-14, MMP-9, TIMP-2, phosphotyrosine, Src, cdc42, cofilin, vinculin, talin, paxillin, tubulin, and in some cases, integrin-αVβ3. All these components are also found in other cellular or cell-associated structures, but their confluence is generally considered indicative of podosomes or invadopodia.
34 35 36 37 38 39 40 However, because of the rapidly evolving structures of podosomes and invadopodia, the relative temporal distributions of these components is not well defined and is probably variable.