FOR 1586:  SKELMET - Mesenchymal and Osteogenic Signalling Pathways in Malignant Bone Diseases

• Subject Area: Medicine
• Term: from 2011 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 179902948

Bone metastases cause a significant individual, medical and socio-economical burden and develop in 50–90 percent of malignancies. Thereby, development of skeletal metastasis is a complex, sequential process with diverse molecular, cellular, paracrine and endocrine, immunological and functional facets. The clarification of these mechanisms requires both, excellent osteological and oncological expertise, which needs to be supported by small animal know-how and molecular imaging.
Therefore, the interdisciplinary Research Unit combines its specific clinical, experimental and translational expertise, methods, animal models and technologies to unravel the molecular mechanisms of bone metastases exemplified by the three main osteotropic malignancies: breast and prostate cancer and multiple myeloma (bone marrow cancer).
Our goals are to characterise and/or develop: (1) osteotropic and osteomimicry mechanisms of breast and prostate cancer cells and myeloma cells, (2) the relevance of pro-inflammatory cytokines and WNT ligands for EMT, the skeletal homing and osteopersistence of cancer cells, (3) mechanisms of modulation and alteration of stem cell niches and bone regeneration by breast and prostate carcinoma cells and myeloma cells as well as interaction-specific targets for imaging and treatment, (4) the activation of osteogenic signalling pathways in breast and prostate carcinoma cells (RANKL and WNT signalling) and in myeloma cells (EBF proteins) and (5) molecular and functional imaging of bone metastases using interaction-specific molecular targets.
The systemic and concerted analysis of mechanisms of bone metastasis will produce enhanced knowledge of this complex biological process. It may identify new target molecules for specific and early diagnosis (molecular imaging) and novel treatment (e.g. antibody- or small molecule-based techniques).

• DFG Programme: Research Units

Projects

• 3D imaging approaches for visualization of target biomarkers in bone metastases in vivo (Applicant Glüer, Claus-Christian )
• Anti-myeloma strategies by re-establishing bone regeneration and hematopoietic niches (Applicant Ebert, Regina )
• Central administration and tissue banking (Applicant Hofbauer, Lorenz C. )
• Central administration, tissue banking, and clinical translation. (Applicant Hofbauer, Lorenz C. )
• Determining the supporting mesenchymal cell lineages and their interactions with multiple myeloma (Applicant Kieslinger, Matthias )
• Dickkopf-1 as a critical determinant of malignant bone disease (Applicants Rachner, Tilmann ;  Rauner, Martina )
• Impact of inflammatory mechanisms on osteoblast-metastatic tumor cell interaction (Applicant Trauzold, Anna )
• Interactions of the WNT and RANKL/OPG pathways in osteomimicry of prostate cancer (Applicant Hofbauer, Lorenz C. )
• Modulation of the hematopoietic stem cell niche by micrometastases (Applicant Bornhäuser, Martin )
• Molecular, functional and micro-morphological imaging of bone metastases in vivo (Applicant Glüer, Claus-Christian )
• Molecular mechanisms of inhibition of bone regeration by myeloma cells via conditioning protected stem cell niches (Applicant Schütze, Norbert )
• Role of Wnt5a in the interactions of prostate cancer cells and the bone microenvironment. (Applicant Hofbauer, Lorenz C. )
• T cell interactions within the multiple myeloma niche (Applicant Beilhack, Andreas )

• Spokesperson: Professor Dr. Lorenz C. Hofbauer