2012|13 Annual Report Fraunhofer IGB

6 4 MEDICINE HUMAN 3D LUNG TUMOR MODEL David Fecher M.Sc. Lung tumors, a difﬁcult to treat condition Lung cancer is the most common cancer worldwide and is dif- ﬁcult to treat due to its heterogeneity. Of the numerous types of cancer, lung tumors are the most prevalent [1]. A realistic model, which enables the possibility to study and understand the development and treatment of these tumors, is urgently required. Testing substances for drug development is a complicated and costly process. Of 250 potential compounds in preclini- cal studies, ultimately only one is made commercially available [2]. One reason for this is the absence of a suitable human test system. In pre-clinical studies and basic research on tumors, both cell lines and animals, especially immunosuppressed mice, are used. The small number of usable substances that eventually make their way into the clinical settings demon- strates that the currently used tumor models do not adequate- ly represent the human tumor. Development of a lung cancer test system In the Project Group Oncology, an acellular bowel segment called SIS (small intestinal submucosa) is used as the scaffold for the tumor models. This collagen structure is a derivative of the BioVaSc and can be statically cultured between two metal rings [3]. On this biological support structure, lung tumor cell lines with different genetic backgrounds may be applied to generate a three-dimensional human tumor model. Differentiated model for the clinical testing of therapeutic strategies After 14 days of static culture, a polarized epithelial layer of the tumor cells forms on the three-dimensional matrix. In comparison to two-dimensional culture, the cells have a marked change in the expression of tumor-related proteins, which better reﬂect in vivo tumor conditions. For the treatment of lung tumors which have a mutation of the EGF receptor (EGFR), the EGFR-inhibitor Geﬁtinib is used in the clinic. When applying the Geﬁtinib treatment on the tu- mor cell line in our model, which includes an active EGFR mu- tation, we get a similar response to what is seen in patients. The proliferation of the tumor cells is inhibited, while more tu- mor cells go through apoptosis. Co-culture with tumor-associated cell types increased complexity of the model In addition to tumor cells, the tumor also has non-tumorous cells and connective tissue, which are referred to as tumor stroma. Tumor-associated ﬁbroblasts are a major component of the tumor stroma and play a signiﬁcant role in tumor devel- opment and progression. To reﬂect this complexity in the in vitro tumor model, estab- lished tumor cell lines were co-cultured with tumor-associated ﬁbroblasts, which were obtained from biopsies of lung can- cer patients. Thus, the inﬂuence of these ﬁbroblasts and their therapeutic potential can be examined as targets for new drugs. 1 2 3

2012|13 Annual Report Fraunhofer IGB

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