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@ARTICLE{Dubash:125736,
      author       = {T. D. Dubash$^*$ and C. M. Hoffmann$^*$ and F. Oppel$^*$
                      and K. Giessler$^*$ and S. Weber$^*$ and S. Dieter$^*$ and
                      J. Hüllein$^*$ and T. Zenz$^*$ and F. Herbst$^*$ and C.
                      Scholl$^*$ and W. Weichert$^*$ and W. Werft and A.
                      Benner$^*$ and M. Schmidt$^*$ and M. Schneider and H.
                      Glimm$^*$ and C. Ball$^*$},
      title        = {{P}henotypic differentiation does not affect tumorigenicity
                      of primary human colon cancer initiating cells.},
      journal      = {Cancer letters},
      volume       = {371},
      number       = {2},
      issn         = {0304-3835},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2017-01862},
      pages        = {326 - 333},
      year         = {2016},
      abstract     = {Within primary colorectal cancer (CRC) a subfraction of all
                      tumor-initiating cells (TIC) drives long-term progression in
                      serial xenotransplantation. It has been postulated that
                      efficient maintenance of TIC activity in vitro requires
                      serum-free spheroid culture conditions that support a
                      stem-like state of CRC cells. To address whether
                      tumorigenicity is indeed tightly linked to such a stem-like
                      state in spheroids, we transferred TIC-enriched spheroid
                      cultures to serum-containing adherent conditions that should
                      favor their differentiation. Under these conditions, primary
                      CRC cells did no longer grow as spheroids but formed an
                      adherent cell layer, up-regulated colon epithelial
                      differentiation markers, and down-regulated TIC-associated
                      markers. Strikingly, upon xenotransplantation cells cultured
                      under either condition equally efficient formed serially
                      transplantable tumors. Clonal analyses of individual
                      lentivirally marked TIC clones cultured under either culture
                      condition revealed no systematic differences in contributing
                      clone numbers, indicating that phenotypic differentiation
                      does not select for few individual clones adapted to
                      unfavorable culture conditions. Our results reveal that CRC
                      TIC can be propagated under conditions previously thought to
                      induce their elimination. This phenotypic plasticity allows
                      addressing primary human CRC TIC properties in experimental
                      settings based on adherent cell growth.},
      keywords     = {Biomarkers, Tumor (NLM Chemicals)},
      cin          = {C060 / G102 / G100 / L101 / G250 / L701},
      ddc          = {570},
      cid          = {I:(DE-He78)C060-20160331 / I:(DE-He78)G102-20160331 /
                      I:(DE-He78)G100-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)G250-20160331 / I:(DE-He78)L701-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26679053},
      doi          = {10.1016/j.canlet.2015.11.037},
      url          = {https://inrepo02.dkfz.de/record/125736},
}