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@ARTICLE{Liu:127963,
      author       = {L. Liu$^*$ and E. Aleksandrowicz$^*$ and P. Fan$^*$ and F.
                      Schönsiegel$^*$ and Y. Zhang$^*$ and H. Sähr and J.
                      Gladkich$^*$ and J. Mattern$^*$ and D. Depeweg and B. Lehner
                      and J. Fellenberg and I. Herr$^*$},
      title        = {{E}nrichment of c-{M}et+ tumorigenic stromal cells of giant
                      cell tumor of bone and targeting by cabozantinib.},
      journal      = {Cell death $\&$ disease},
      volume       = {5},
      number       = {10},
      issn         = {2041-4889},
      address      = {London [u.a.]},
      publisher    = {Nature Publishing Group},
      reportid     = {DKFZ-2017-03985},
      pages        = {e1471},
      year         = {2014},
      abstract     = {Giant cell tumor of bone (GCTB) is a very rare tumor
                      entity, which is little examined owing to the lack of
                      established cell lines and mouse models and the restriction
                      of available primary cell lines. The stromal cells of GCTB
                      have been made responsible for the aggressive growth and
                      metastasis, emphasizing the presence of a cancer stem cell
                      population. To identify and target such tumor-initiating
                      cells, stromal cells were isolated from eight freshly
                      resected GCTB tissues. Tumorigenic properties were examined
                      by colony and spheroid formation, differentiation,
                      migration, MTT
                      (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
                      bromide) assay, immunohistochemistry, antibody protein
                      array, Alu in situ hybridization, FACS analysis and
                      xenotransplantation into fertilized chicken eggs and mice. A
                      sub-population of the neoplastic stromal cells formed
                      spheroids and colonies, differentiated to osteoblasts,
                      migrated to wounded regions and expressed the metastasis
                      marker CXC-chemokine receptor type 4, indicating
                      self-renewal, invasion and differentiation potential.
                      Compared with adherent-growing cells, markers for
                      pluripotency, stemness and cancer progression, including the
                      CSC surface marker c-Met, were enhanced in spheroidal cells.
                      This c-Met-enriched sub-population formed xenograft tumors
                      in fertilized chicken eggs and mice. Cabozantinib, an
                      inhibitor of c-Met in phase II trials, eliminated CSC
                      features with a higher therapeutic effect than standard
                      chemotherapy. This study identifies a c-Met(+) tumorigenic
                      sub-population within stromal GCTB cells and suggests the
                      c-Met inhibitor cabozantinib as a new therapeutic option for
                      targeted elimination of unresectable or recurrent GCTB.},
      keywords     = {Anilides (NLM Chemicals) / Biomarkers, Tumor (NLM
                      Chemicals) / Pyridines (NLM Chemicals) / cabozantinib (NLM
                      Chemicals) / Proto-Oncogene Proteins c-met (NLM Chemicals)},
      cin          = {G403},
      ddc          = {570},
      cid          = {I:(DE-He78)G403-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25321478},
      pmc          = {pmc:PMC4237261},
      doi          = {10.1038/cddis.2014.440},
      url          = {https://inrepo02.dkfz.de/record/127963},
}