Table IV.
Targeting molecular mechanisms that support cell-matrix interactions.
| Target | Molecular Mechanism | Reference |
|---|---|---|
| Integrin αvβ3 | Matrix adhesion receptor of the integrin family involved in the adhesion to a wide variety of matrix components that exhibit the RGD sequence. These include collagen, vitronectin, and fibronectin. This integrin is also extensively expressed by the host vasculature and hemopoietic cells. | [148] |
| Integrin α2β1 | Matrix adhesion receptor of the integrin family involved in the adhesion to collagen and a few additional substrates. While the receptor facilitates motility on collagen it actually inhibits migration on non-collagen substrates and suppresses metastasis. | [77, 172] |
| Syndecan-1 | Transmembrane proteoglycan of the immunoglobulin super family. Syndecans have previously been considered as ligand gatherers, working as co-receptors in collaboration with signalling receptors but they can also signal independently. Syndecan-1 interacts with the ECM through its glycosaminoglycan side chains. Some reports suggest it can also engage in cell-cell adhesion. Loss of Syndecan-1 is specifically associated with metastasis. | [149–151] |
| MMP14 | Transmembrane metalloproteinase of the MMP family. MMP14 is a collagenase but also capable of cleaving aggrecan, elastin, fibronectin, gelatin, tenascin, nidogen, perlecan, fibrillin, and laminin. It can also cause shedding of Syndecan-1, and betaglycan (TBRIII). It can activate the MMP2 and MMP-13 activation. Its activity can be reguated by ALCAM and CD151. MMP14 is expressed in many metastatic cells and facilitates invasion. However, it is not required for metastasis. | [170, 171] |
| CD44 | Transmembrane receptor for hyaluronic acid and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). Splice variant expression is correlated with motility and metastasis. Splice variant-induced changes in adhesion can facilitate migration and metastasis. | [152, 153] |
Molecules included here are representative molecular determinants of the underlying principle