Matrix metalloproteinase-2 is involved in A549 cell migration on laminin-10/11.
We have reported that laminin-10/11 strongly promotes migration of A549 human lung carcinoma cells by activating the alpha3beta1 integrin-dependent signaling pathway. To elucidate the mechanism involved, we investigated whether matrix metalloproteinases (MMPs) are involved in cell migration on laminin-10/11. Here, we demonstrate that laminin-10/11, but not fibronectin which does not greatly promote A549 cell movement, stimulated MMP-2 secretion approximately 3-fold. The cell migration-promoting activity of laminin-10/11 was down-regulated by an MMP inhibitor. In addition, cell motility was significantly increased when cells adhered to a mixture of fibronectin and laminin-10/11 with a concomitant decrease of focal contacts, compared with those adhering to fibronectin alone. The enhanced cell migration was partially suppressed by the MMP inhibitor. Furthermore, an anti-alpha3 integrin, but not an anti-alpha5 integrin, antibody induced the activated form of MMP-2. These data suggest that MMP-2 may play an important role in A549 cell migration on laminin-10/11 through an alpha3beta1 integrin-dependent pathway.
Gu
J
J
Division of Protein Chemistry, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, 565-0871, Osaka, Japan. jgu@protien.osaka-u.ac.jp
Nishiuchi
R
R
Sekiguchi
K
K
D000906:Antibodies / Q000276:immunology; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000276:immunology; D007797:Laminin / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D061965:Matrix Metalloproteinase Inhibitors; D008856:Microscopy, Fluorescence; D011480:Protease Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D039201:Integrin alpha3beta1; D016023:Integrins; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; C119013:laminin 10; D020778:Matrix Metalloproteinase 2