Laminin-binding integrins in tumor progression and metastasis.

Interactions between tumor cells and extracellular matrix occur at several points during the metastatic cascade. Epithelial tumors, which represent nearly 90% of human neoplasia, must invade their underlying basement membrane to enter the interstitial stroma. For distant metastasis, malignant cells must penetrate basement membranes to gain access to blood vessels and organ parenchyma. Integrin receptors that bind to multiple laminin isoforms appear to mediate tumor cell adhesion to basement membranes before and during invasion. It is notable that changes in several laminin-binding integrins occur during tumor progression. These changes may include increased or decreased expression, or changes in distribution from a polarized to a dispersed pattern. Integrins not only mediate cell adhesion and motility but also transduce important downstream signaling events that regulate cell growth, survival, and gene expression. During tumor progression, the development of variant cells with changes in integrin expression and the associated signaling pathways could result in cells with a highly invasive and metastatic phenotype.