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

Cell Mol Life Sci. 2005 Apr;62(7-8):870-80. doi: 10.1007/s00018-005-4478-8.


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 gamma2 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 beta4-integrin-dependent signaling on the HaCaT-EA matrix toward alpha3-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 gamma2 chains leads to the integrin switch favoring epithelial migration and that MMP-19 actively participates in the early stages of SCC invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / physiology*
  • Cells, Cultured
  • Collagen Type IV / metabolism
  • Epidermal Cells
  • Epidermis / metabolism
  • Fibrin / metabolism
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Laminin / metabolism*
  • Matrix Metalloproteinases, Secreted
  • Metalloendopeptidases / metabolism*
  • Neoplasm Invasiveness
  • Neoplasms, Squamous Cell / metabolism*
  • Neoplasms, Squamous Cell / pathology
  • Phosphotyrosine / metabolism


  • Collagen Type IV
  • LAMC2 protein, human
  • Laminin
  • Phosphotyrosine
  • Fibrin
  • Matrix Metalloproteinases, Secreted
  • Metalloendopeptidases
  • matrix metalloproteinase 19