For a better understanding of metastasis, systematic analyses are essential. We aim to achieve this by closely linking the various subprojects via central mouse models and novel, shared technology platforms. We will use the BalbNeuT model, including genetic modifications of it, also in the second funding period. With these models we strive to identify the impact of metastatic target organs as well as systemically acting (immune-) mechanisms on the outgrowth of metastasis. The central goal of FOR 2127 - to proceed from animal models towards a mechanistic analysis of human cancer - will be addressed by the implementation of novel technologies. We aim to investigate interactions between colony-forming cancer cells and target organs initially in murine tissue cultures and subsequently in human tissues. For this we will establish the precision cut tissue slice (PCTS) culture in C1 and provide it for the subprojects. The technology is firmly established at the Fraunhofer institute ITEM in Hannover, has been improved continously and will be transferred to Regensburg. By PCTS technology tissue sections of about 300 µm can be cultured and exposed to various conditions. In collaboration with C2, C1 will extend the power of PCTS by adding spatial transcriptomic analysis as downstream application, which allows to link morphological, functional and transcriptomic information of the tissue slices. Combining these technologies and applying it to various questions of the subprojects we aim to address important questions of early metastasis formation in a way that has not been possible with human tissues so far.
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