Etablierung der Organotypischen Hirnschnitt-Kokultur als Tumor-Invasionsmodell

Abstract

The aim of this study is to contribute significantly to our understanding of cerebral metastasis formation. The process of the metastatic site has barely been investigated yet, in particular the role of resident cells. It is already known that Tumor-Associated-Macrophages (TAM) support migration, invasion and proliferation. Interestingly the cardinal organs of metastasis possess tissue specialized macrophages, such as Osteoclasts in the bone marrow, Kupffer cells in the liver or microglia in the brain. In this context we focus on the influence of microglia as specialized resident macrophages on the cerebral metastasis formation of breast cancer cells. Modifying the previously published organotypic brain slice approach as a coculture between brain tissue and an epithelial breast cancer cell line, it was possible to demonstrate the interactions between cancer cells and microglia. In doing so the assumption that microglia enhance invasion and colonization of brain tissue by breast cancer cells could be emphasized. Surprisingly microglia thereby serve both as active transporters and guiding rails for the epithelial cancer cell. The organotypic brain slice coculture is a novel established method highly suitable for analysing metastasis formation, invasion, colonization and the corresponding cell to cell interaction by fluorescence and bright field microscopy. In this regard the brain slice coculture model has a strong potential for a wide variety of putative applications and analysis. Nevertheless there remain prospects to achieve improvement, such as 1. Verifying the viability of the brain slice tissue 2. Quantification of the tumor cell invasion 3. Conducting the coculture with a cancer cell line of murine origin. Furthermore the understanding of the interactions between cancer cells and the resident compartment could have helpful implications for the treatment of patients, for example in brain surgery or the use of drugs inhibiting macrophage activity.