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@ARTICLE{Bingel:128001,
      author       = {C. Bingel$^*$ and E. Koeneke$^*$ and J. Ridinger$^*$ and A.
                      Bittmann$^*$ and M. Sill$^*$ and H. Peterziel$^*$ and J.
                      Wrobel$^*$ and I. Rettig$^*$ and T. Milde$^*$ and U.
                      Fernekorn and F. Weise and A. Schober and O. Witt$^*$ and I.
                      Oehme$^*$},
      title        = {{T}hree-dimensional tumor cell growth stimulates autophagic
                      flux and recapitulates chemotherapy resistance.},
      journal      = {Cell death $\&$ disease},
      volume       = {8},
      number       = {8},
      issn         = {2041-4889},
      address      = {London [u.a.]},
      publisher    = {Nature Publishing Group},
      reportid     = {DKFZ-2017-04023},
      pages        = {e3013},
      year         = {2017},
      abstract     = {Current preclinical models in tumor biology are limited in
                      their ability to recapitulate relevant (patho-)
                      physiological processes, including autophagy.
                      Three-dimensional (3D) growth cultures have frequently been
                      proposed to overcome the lack of correlation between
                      two-dimensional (2D) monolayer cell cultures and human
                      tumors in preclinical drug testing. Besides 3D growth, it is
                      also advantageous to simulate shear stress, compound flux
                      and removal of metabolites, e.g., via bioreactor systems,
                      through which culture medium is constantly pumped at a flow
                      rate reflecting physiological conditions. Here we show that
                      both static 3D growth and 3D growth within a bioreactor
                      system modulate key hallmarks of cancer cells, including
                      proliferation and cell death as well as macroautophagy, a
                      recycling pathway often activated by highly proliferative
                      tumors to cope with metabolic stress. The autophagy-related
                      gene expression profiles of 2D-grown cells are substantially
                      different from those of 3D-grown cells and tumor tissue.
                      Autophagy-controlling transcription factors, such as TFEB
                      and FOXO3, are upregulated in tumors, and 3D-grown cells
                      have increased expression compared with cells grown in 2D
                      conditions. Three-dimensional cultures depleted of the
                      autophagy mediators BECN1, ATG5 or ATG7 or the transcription
                      factor FOXO3, are more sensitive to cytotoxic treatment.
                      Accordingly, combining cytotoxic treatment with compounds
                      affecting late autophagic flux, such as chloroquine, renders
                      the 3D-grown cells more susceptible to therapy. Altogether,
                      3D cultures are a valuable tool to study drug response of
                      tumor cells, as these models more closely mimic tumor
                      (patho-)physiology, including the upregulation of tumor
                      relevant pathways, such as autophagy.},
      cin          = {G340 / B062 / C060},
      ddc          = {570},
      cid          = {I:(DE-He78)G340-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)C060-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28837150},
      pmc          = {pmc:PMC5596581},
      doi          = {10.1038/cddis.2017.398},
      url          = {https://inrepo02.dkfz.de/record/128001},
}