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@ARTICLE{Depner:119865,
      author       = {S. Depner$^*$ and W. Lederle and C. Gutschalk$^*$ and N.
                      Linde$^*$ and A. Zajonz$^*$ and M. M. Mueller$^*$},
      title        = {{C}ell type specific interleukin-6 induced responses in
                      tumor keratinocytes and stromal fibroblasts are essential
                      for invasive growth.},
      journal      = {International journal of cancer},
      volume       = {135},
      number       = {3},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2017-00460},
      pages        = {551-562},
      year         = {2014},
      abstract     = {Interleukin-6 (IL-6) is one of the major inflammatory
                      interleukins that has been linked to cancer progression. In
                      our model for human skin squamous cell carcinoma (SCC), IL-6
                      expression is strongly upregulated upon progression from
                      benign tumors to highly malignant, metastasizing SCCs. We
                      now demonstrate that IL-6 promotes malignant and invasive
                      tumor growth in human skin SCCs by inducing cell type
                      specific cytokine profiles in tumor keratinocytes and
                      stromal fibroblasts, activating the latter towards a tumor
                      associated fibroblast (TAF) phenotype. In three-dimensional
                      organotypic cocultures in vitro invasive growth of IL-6
                      overexpressing tumor keratinocytes, is associated with
                      increased expression of matrix metalloproteinase-2 (MMP-2),
                      MMP-14 and tissue inhibitor of metalloproteinases-2, and
                      clearly depends on IL-6 activated fibroblasts. IL-6-induced
                      secretion of monocyte chemotactic protein-1 (MCP-1) in tumor
                      keratinocytes and of hepatocyte growth factor in fibroblasts
                      is crucial for regulating expression and activation of
                      MMP-2. This functional role of IL-6 is confirmed in vivo.
                      Here MMP-14 and MMP-2 expression occur exclusively in
                      surface transplants of IL-6 overexpressing keratinocytes and
                      fibroblasts are identified as important source of MMP-2. Our
                      data indicate that tumor keratinocytes derived IL-6
                      activates stromal fibroblasts towards a TAF phenotype,
                      promoting tumor invasion via enhanced expression and
                      activation of MMP-2.},
      keywords     = {Culture Media, Conditioned (NLM Chemicals) / Interleukin-6
                      (NLM Chemicals) / MMP2 protein, human (NLM Chemicals) /
                      Matrix Metalloproteinase 2 (NLM Chemicals)},
      cin          = {A150},
      ddc          = {610},
      cid          = {I:(DE-He78)A150-20160331},
      pnm          = {311 - Signalling pathways, cell and tumor biology
                      (POF3-311)},
      pid          = {G:(DE-HGF)POF3-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:23165423},
      url          = {https://inrepo02.dkfz.de/record/119865},
}