Detection and Inhibition of Undesirable Tumour-Promotion by Non-Transformed Stroma Cells

Background: Only recently it was recognized that cancer cells may receive active support by microenvironmental stromal cells via secreted growth factors and other tumour promoters. Our aim is to establish therapeutic strategies to specifically suppress such undesirable cell activities. Up until now, no standard assay has been established for quantifying such tumor promoting molecules. With our assays based on targeted proteomics, we have developed assays for this purpose. We are currently identifying and quantifying relevant tumor promoters in cell culture models as well as in blood samples. These assays allow us now to screen for drugs which suppress such tumour-supporting activities and may be used for patient treatment.

Methods and Models: Molecular profiling (I, II), targeted analyses (III) and cell culture (IV). Several kinds of leukemia cells, e.g. from Chronic Lymphatic Leukemia and Multiple Myeloma are strongly dependent on the microenvironmental support and would die spontaneously without that support. Therefore these still incurable B-cell malignancies are ideal model systems for our research. We isolate and analyse tumour cells from patients and optionally co-culture them with primary bone marrow-derived stromal cells for subsequent treatment and investigations.

Aims: We want to find drugs specifically interfering with undesirable stromal cell activities by monitoring tumor promoter secretion using our analytical assays. It is our great aim to test such active compounds in clinical trials with the hope that successful pre-treatment of stromal cells would render a following chemotherapeutic treatment less toxic and more efficient.

Collaboration partners and funding:

• Univ.-Prof. Dr. Dr.h.c. Christoph Zielinski, Chairman, Clinical Division of Oncology and Department of Medicine I, Chairman, Comprehensive Cancer Center Medical University Vienna - General Hospital Vienna, Austria

• Prof. Dr. Hermine Agis, Department of Medicine I, Medical University of Vienna.

• Prof. Dr. Peter and Dr. Ingeborg Ambros, Children’s Cancer Research Institute, Vienna

• Prof. Dr. Josef Schwarzmeier, Karl Landsteiner Institute for Bioanalytical Oncology.

• Prof. Dr. Verena Paulitschke, Department of General Dermatology, Medical University of Vienna
  
  

This project is supported by:

• Austrian Research Fund fwf

• Austrian Research Promotion Agency (FFG)

• Bürgermeisterfond of Vienna

• Initiative Krebsforschung

• Karl Fellinger Foundation