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@ARTICLE{Meides:127935,
      author       = {A. Meides$^*$ and C. M. Gutschalk$^*$ and L. Devel and F.
                      Beau and B. Czarny and S. Hensler and J. Neugebauer$^*$ and
                      V. Dive and P. Angel$^*$ and M. M. Mueller$^*$},
      title        = {{E}ffects of selective {MMP}-13 inhibition in squamous cell
                      carcinoma depend on estrogen.},
      journal      = {International journal of cancer},
      volume       = {135},
      number       = {12},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2017-03957},
      pages        = {2749 - 2759},
      year         = {2014},
      abstract     = {Matrix metalloproteinases like MMP-13 cleave and remodel
                      the extracellular matrix and thereby play a crucial role in
                      tumor progression in vivo. Using a highly selective
                      inhibitor to block MMP-13 protein activity, we demonstrate a
                      striking inhibitory effect on invasive tumor growth and
                      vascularization in murine skin squamous cell carcinoma
                      (SCC). Therapy outcome critically depends on animal age in
                      C57Bl/6 mice and was successful in old female but not in
                      young female mice. Treatment success was recovered by
                      ovariectomy in young and abolished by 17ß-estradiol
                      supplementation in old mice, suggesting a hormone dependent
                      inhibitor effect. Responsiveness of the tumorigenic
                      keratinocytes BDVII and fibroblasts to 17ß-estradiol was
                      confirmed in vitro, where MMP-13 inhibitor treatment led to
                      a reduction of cell invasion and vascular endothelial growth
                      factor (VEGF) release. This correlated well with a less
                      invasive and vascularized tumor in treated mice in vivo.
                      17ß-estradiol supplementation also reduced invasion and
                      VEGF release in vitro with no additional reduction on MMP-13
                      inhibitor treatment. This suggests that low 17ß-estradiol
                      levels in old mice in vivo lead to enhanced MMP-13 levels
                      and VEGF release, allowing a more effective inhibitor
                      treatment compared to young mice. In our study, we present a
                      strong link between lower estrogen levels in old female
                      mice, an elevated MMP-13 level, which results in a more
                      effective MMP-13 inhibitor treatment in fibroblasts and SCC
                      cells in vitro and in vivo.},
      keywords     = {Estrogens (NLM Chemicals) / Matrix Metalloproteinase
                      Inhibitors (NLM Chemicals) / Vascular Endothelial Growth
                      Factor A (NLM Chemicals) / Estradiol (NLM Chemicals) /
                      Matrix Metalloproteinase 13 (NLM Chemicals)},
      cin          = {A101 / A100},
      ddc          = {610},
      cid          = {I:(DE-He78)A101-20160331 / I:(DE-He78)A100-20160331},
      pnm          = {311 - Signalling pathways, cell and tumor biology
                      (POF3-311)},
      pid          = {G:(DE-HGF)POF3-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:24676718},
      doi          = {10.1002/ijc.28866},
      url          = {https://inrepo02.dkfz.de/record/127935},
}