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- Title
Matrix metalloproteinase 19 processes the laminin 5 gamma 2 chain and induces epithelial cell migration.
- Authors
Sadowski, T.; Dietrich, S.; Koschinsky, F.; Ludwig, A.; Proksch, E.; Titz, B.; Sedlacek, R.
- Abstract
In this study we analyzed the proteolytic activity of MMP-19 and its impact on keratinocyte migration. In the HaCaT keratinocyte cell line overexpressing wild-type MMP-19 (HaCaT-WT), transmigration through fibrin and type IV collagen matrices was significantly increased compared to cells harboring a catalytically inactive mutant (HaCaT-EA). Studying the expression of MMP-19 in early stages of squamous cell cancer (SCC), we found co-localization of MMP-19 and laminin 5 at the invading tumor front but not in suprabasal epidermis of the tumor. Examination of laminin 5 processing revealed increased processing of the ?2 chain in the medium and matrix of HaCaT-WT cells and degradation by recombinant human MMP-19 to 105-kDa and 80-kDa fragments. Parental HaCaT grown on the matrix of HaCaT-WT and HaCaT-EA cells displayed differential tyrosine phosphorylation. Using integrin blocking and stimulating antibodies we could attribute these differences to a shift from ß4-integrin-dependent signaling on the HaCaT-EA matrix toward a3-integrin-dependent signaling on the HaCaT-WT matrix. As a consequence, parental HaCaT showed increased migration on the matrix of HaCaT-WT cells. These data suggest that the MMP-19-dependent processing of the ?2 chains leads to the integrin switch favoring epithelial migration and that MMP-19 actively participates in the early stages of SCC invasion.
- Subjects
METALLOPROTEINASES; CELL migration; EXTRACELLULAR matrix; SQUAMOUS cell carcinoma; KERATINOCYTES; TUMORS
- Publication
Cellular & Molecular Life Sciences, 2005, Vol 62, Issue 7/8, p870
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-005-4478-8