Matrilysin 1 Influences Colon Carcinoma Cell Migration by Cleavage of the Laminin-5 β3 Chain

摘要: Matrilysin 1 [matrix metalloproteinase 7 (MMP7)] is one of the most important metalloproteinases expressed in human tissues. This enzyme generally not by normal differentiated epithelial colon cells, but has been shown to be up-regulated adenomas and adenocarcinomas. Little known about role MMP7 cell invasion its involvement proteolytic processes. By searching ligands colonic carcinoma cells HT29, we identified laminin-5/laminin-332 (LN5) as a specific target for enzymatic activity. LN5, composed alpha3, beta3, gamma2 chains, an component basement membranes where it induces firm adhesion hemidesmosome formation. In this study, show that LN5 are coexpressed HT29 well xenograft tumors colorectal We provide evidence ligand cleavage occurs beta3 chain, giving rise carboxyl-terminal chain fragment 90 kDa. have site at position Ala(515)-Ile(516) chain. Videomicroscopic analysis plated on substrates reveals MMP7-processed significantly enhances motility. Moreover, delayed migration obtained after inhibition reinforces hypothesis supporting migration. Altogether, our results likely play crucial regulation targeting processing