Laminin (Mr=900,000) is a large glycoprotein specific to basement membranes. Laminin has been shown to promote cell adhesion, cell growth, cell migration, neurite outgrowth, cell differentiation, and to influence the metastatic behavior of tumor cells. Laminin binds to type IV collagen, heparin, gangliosides, and cell surface receptors and promotes the adhesion and growth of various epithelial and tumor cells as well as neurite outgrowth. Laminin is thought to mediate cell-matrix interactions and to be a structural component of all basement membranes binding to collagen IV, heparan sulfate proteoglycan, and nidogen-entactin.
The laminin molecule itself has a cross-like shape when examined by microscopy, with three short arms and one long arm. Two small globules can be observed at the end of each short arm, and a larger globule can be observed at the end of the long arm. Current models suggest that laminin contains one A chain (Mr=440,000), one B1 chain (Mr=225,000), and one B2 chain (Mr=205,000), with part of each chain forming a short arm and the rest of the chain projecting down the long arm.
Laminin exhibits a number of biological activities, including promoting the attachment, migration, and differentiation of certain cells. Some progress has been made in assigning domains in laminin to its activities. Collagen IV binding is attributed to the globules at the end of the short arm. Cell binding is attributed to the portion of laminin minus the long arm and globules. A site in the long arm of laminin is thought to promote axonal outgrowth. Most of the alpha-helical elements in the laminin molecule have been localized to the portion of the long arm adjacent to the terminal globule. The size of the molecule plus difficulty in separating its chains have impeded further characterization of laminin's structure by conventional chemical approaches.
Active domains have been localized in laminin, based on recent progress in cloning the laminin chains. The B1 chain comprises some 1786 amino acids which appear to form at least six contiguous structural domains. Domains I and II are predominantly alpha-helical and probably extend down the long arm. Domains III and V contain homologous repeats rich in cysteine, and could form rather rigid structures adjacent to the globules formed by domains IV and VI. Studies by the present inventors indicate that a sequence of some five to nine amino acids in domain III is at least partly responsible for the cell attachment, chemotactic, and receptor binding activities of laminin. This sequence also has antimetastatic activity with tumor cells.