Cellular and Molecular Life Sciences CMLS

, Volume 62, Issue 7–8, pp 870–880

Matrix metalloproteinase 19 processes the laminin 5 gamma 2 chain and induces epithelial cell migration

  • T. Sadowski
  • S. Dietrich
  • F. Koschinsky
  • A. Ludwig
  • E. Proksch
  • B. Titz
  • R. Sedlacek
Research Article

DOI: 10.1007/s00018-005-4478-8

Cite this article as:
Sadowski, T., Dietrich, S., Koschinsky, F. et al. CMLS, Cell. Mol. Life Sci. (2005) 62: 870. doi:10.1007/s00018-005-4478-8

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 γ2 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 β4-integrin-dependent signaling on the HaCaT-EA matrix toward α3-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 γ2 chains leads to the integrin switch favoring epithelial migration and that MMP-19 actively participates in the early stages of SCC invasion.

Key words.

Matrix metalloproteinase extracellular matrix laminin tumor invasion integrin signaling keratinocyte 

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Copyright information

© Birkhäuser Verlag, Basel 2005

Authors and Affiliations

  • T. Sadowski
    • 1
    • 3
  • S. Dietrich
    • 1
  • F. Koschinsky
    • 1
  • A. Ludwig
    • 1
  • E. Proksch
    • 2
  • B. Titz
    • 1
  • R. Sedlacek
    • 1
  1. 1.Institute of BiochemistryUniversity of KielKielGermany
  2. 2.Department of DermatologyUniversity of KielKielGermany
  3. 3.DI&A DG CardiovascularAventis Pharma Deutschland GmbHFrankfurtGermany

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