@article{FecherHofmannBucketal.2016,
  author    = {Fecher, David and Hofmann, Elisabeth and Buck, Andreas and Bundschuh, Ralph and Nietzer, Sarah and Dandekar, Gudrun and Walles, Thorsten and Walles, Heike and L{\"u}ckerath, Katharina and Steinke, Maria},
  title     = {Human Organotypic Lung Tumor Models: Suitable For Preclinical \(^{18}\)F-FDG PET-Imaging},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0160282},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179678},
  year      = {2016},
  abstract  = {Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and -testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[\(^{18}\)F]fluoro-D-glucose positron emission tomography (FDG-PET) these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future.},
  language  = {en}
}
@article{NietzerBaurSieberetal.2016,
  author    = {Nietzer, Sarah and Baur, Florentin and Sieber, Stefan and Hansmann, Jan and Schwarz, Thomas and Stoffer, Carolin and H{\"a}fner, Heide and Gasser, Martin and Waaga-Gasser, Ana Maria and Walles, Heike and Dandekar, Gudrun},
  title     = {Mimicking metastases including tumor stroma: a new technique to generate a three-dimensional colorectal cancer model based on a biological decellularized intestinal scaffold},
  series = {Tissue Engineering Part C-Methods},
  volume    = {22},
  journal   = {Tissue Engineering Part C-Methods},
  number    = {7},
  doi       = {10.1089/ten.tec.2015.0557},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188202},
  pages     = {621-635},
  year      = {2016},
  abstract  = {Tumor models based on cancer cell lines cultured two-dimensionally (2D) on plastic lack histological complexity and functionality compared to the native microenvironment. Xenogenic mouse tumor models display higher complexity but often do not predict human drug responses accurately due to species-specific differences. We present here a three-dimensional (3D) in vitro colon cancer model based on a biological scaffold derived from decellularized porcine jejunum (small intestine submucosa+mucosa, SISmuc). Two different cell lines were used in monoculture or in coculture with primary fibroblasts. After 14 days of culture, we demonstrated a close contact of human Caco2 colon cancer cells with the preserved basement membrane on an ultrastructural level as well as morphological characteristics of a well-differentiated epithelium. To generate a tissue-engineered tumor model, we chose human SW480 colon cancer cells, a reportedly malignant cell line. Malignant characteristics were confirmed in 2D cell culture: SW480 cells showed higher vimentin and lower E-cadherin expression than Caco2 cells. In contrast to Caco2, SW480 cells displayed cancerous characteristics such as delocalized E-cadherin and nuclear location of beta-catenin in a subset of cells. One central drawback of 2D cultures-especially in consideration of drug testing-is their artificially high proliferation. In our 3D tissue-engineered tumor model, both cell lines showed decreased numbers of proliferating cells, thus correlating more precisely with observations of primary colon cancer in all stages (UICC I-IV). Moreover, vimentin decreased in SW480 colon cancer cells, indicating a mesenchymal to epithelial transition process, attributed to metastasis formation. Only SW480 cells cocultured with fibroblasts induced the formation of tumor-like aggregates surrounded by fibroblasts, whereas in Caco2 cocultures, a separate Caco2 cell layer was formed separated from the fibroblast compartment beneath. To foster tissue generation, a bioreactor was constructed for dynamic culture approaches. This induced a close tissue-like association of cultured tumor cells with fibroblasts reflecting tumor biopsies. Therapy with 5-fluorouracil (5-FU) was effective only in 3D coculture. In conclusion, our 3D tumor model reflects human tissue-related tumor characteristics, including lower tumor cell proliferation. It is now available for drug testing in metastatic context-especially for substances targeting tumor-stroma interactions.},
  language  = {en}
}