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Mechanisms of Tumor Cell Invasion

Dr. Björn Tews

DKFZ-ZMBH Alliance

German Cancer Research Center

Im Neuenheimer Feld 581

69120 Heidelberg, Germany

Analyzing lipid profiles of different glioma cell populations and signaling of related G-protein coupled receptors is a main part of our research. The ultimate goal is to identify the functional consequences of these deregulated signaling cascades on tumor cell migration and invasion.

Glioblastoma is the most aggressive brain tumor with a poor prognosis reflected by a median patient survival of about 14 months. The invasive nature of glioma cells mainly accounts for their resistance to current treatment modalities, as the diffusely infiltrating tumor cells, which evade surgical resection and survive treatment, inevitably give rise to reoccurring tumors. Substantial evidence has been accumulated to suggest that lysophospholipids are involved in tumorigenesis; they are especially important for therapeutic resistance of tumors by regulating tumor cell migration. We investigate lysophospholipid signaling depending on the extracellular matrix environment and determine the consequences of different regimens of in vitro and in vivo chemotherapy. Analyzing lipid profiles of different glioma cell populations and signaling of related G-protein coupled receptors is a main part of our research. The ultimate goal is to identify the functional consequences of these deregulated signaling cascades on tumor cell migration and invasion. Our methodological repertoire includes modulation of GPCR expression and signaling, different in vitro paradigms to study cell migration and invasion such as organotypic slice cultures, Real-time Cell Analyses (RTCA), time-lapse microscopy and in vivo xenografting techniques combined with imaging of tumor cells in different transgenic mouse lines.

Understanding the complex lysophospholipid signaling cascades upon different treatments will provide important information to design new tailored therapies for patients suffering from glioma by combining established chemotherapeutics with the application of sphingolipid-modulating antibodies and small molecules.