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Projekt
The role of host cell-tumor cell interaction for beta-catenin mediated tumor cell invasion in colorectal liver metastases
Antragsteller
Privatdozent Dr. Karsten Brand
Fachliche Zuordnung
Allgemein- und Viszeralchirurgie
Förderung
Förderung von 2009 bis 2015
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 101804013
Successful metastasis requires invasion and unlimited growth potential, which are tumor cell properties associated with epithelial mesenchymal transition (EMT) and stemness, respectively. The stromal derived microenvironment seems to be involved in both properties by acting in a paracrine fashion on the tumor cells. Beta-catenin is a crucial molecule in EMT and stemness. So far, nearly 100 binding partners of nuclear β-catenin have been described, some of which are regulated by host cells. In this project we propose to examine the influence of tumor cell/host cell interaction on EMT and stemness in the invasion front of colorectal liver metastases. Our main indicator molecule for these processes is ß-catenin which is nuclearly localized in the tumor cells of the invasion front and has been found by us to be transcriptionally activated. Within this application for a second funding period, we will continue our identification and further characterization of molecules secreted by host cells, acting on tumor cells finally leading to activation of the ß-catenin promoter. Candidate molecules determined during the first funding period will be validated in ex vivo assays and new candidates will be determined by microdissection and differential gene expression of stromal components. In addition, we will continue our correlation of the spatial and intracellular distribution of β-catenin mRNA and protein with clinical prognostic parameters. These data will help further elucidating the role of β-catenin in invasion and metastasis and determine new candidate molecules involved in the respective signalling cascades in host cells and tumor cells.
DFG-Verfahren
Klinische Forschungsgruppen
