Anna Neumann
Cancer is one of the most common causes of death world wide and in most cancer patients metastasis is the main cause of death. Osteosarcoma (OS) is the most common primary malignancy of bone, with up to 80% of patients suffering from metastasis or micrometastatic disease at the time of diagnosis. For the metastatic potential of tumours invasiveness plays an important role. The focus of this study is to determine new candidate genes for invasiveness. For that OS cell lines are analysed using a modified Boyden Chamber assay to separate invasive and non-invasive cells. After that total RNA of both fractions is analysed by Illumina hybridisation Arrays (V3 bead arrays). Pair wise comparison (using an S-Plus based evaluation pipeline) yield stable differently expressed genes between invasive and non-invasive cells. These genes are involved in pathways such as cell motility, cell communication or signal transduction. Therefore these candidate genes a) support the established experimental model for metastasis of OS cells and b) give strong clues for a core pattern of metastasis related genes. For functional characterization a combination of knock-down experiments (RNAi) and invasion assay is used. To validate the results RT-PCR and immunohistochemistry on a larger sample using OS-TMAs is processed. Determined genes and pathways are correlated with clinical parameters like metastasis, survival and chemotherapy sensitivity in order to improve the understanding of the biology of OS.