Structure and Function of Laminin-5, a Cell Adhesion Protein of Basement Membrane

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The basement protein laminin-5(LN5), a heterotrimer of laminin α3, β3 and γ2 chains, potently promotes cellular adhesion and motility. In this study, we investigated the structure and function relationship of LN5 and its pathological roles in tumor invasion. 1) The α3 chain of LN5 contains five globular domains (G1 to G5) in its carboxyl end. To clarify the function of each G domain, we transfected cDNAs for the full length and five deletion derivatives of the α3 chain into human HT1080 cells, which express only the laminin β3 andγ2 chains, and prepared recombinant LN5s lacking each G domain. The deletion of G5 or G4-5 did not affect the biological activities of LN5, but the LN5 without G3-5 showed little activities of cell adhesion and migration. It was also found that G3 contained two different regions to stimulate cell adhesion and migration. Furthermore, we found that the α3 chain was cleaved between G3 and G4 after secretion and determined the cleavage site. 2) The 105-kDa γ2 chain of LN5 is cleaved at an amino-terminal region to produce the 105-kDa form. We found that MT1-MMP catalyzed this processing, and that this processing increased the cell motility activity of LN5 but decreased its cell adhesion activity. These results demonstrate that the amino-terminal region of γ2 chain has an important effect on the biological activity of LN5. 3) Immunohistochemical analysis showed that the laminin γ2 chain monomer was overexpressed in invading human carcinoma cells. When a cDNA for the amino-terminal regions of the γ2 chain was transfected into a human carcinoma cell line, the invasive potential of this cell line in vivo was greatly enhanced. These results suggest that the γ2 chain itself plays some important roles in tumor invasion.