SPP 2084:  µBONE: Colonization and interaction of tumor cells within the bone microenvironment

• Subject Area: Medicine ; Biology
• Term: from 2018 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 359040200

Interdisciplinary collaboration, scientific exchange, integration of early career scientists, and clinical translation were key components for success of the SPP2084. Active communication turned out to be essential for effective networking. This required regular face-to-face meetings at annual retreats, symposia, and workshops as well as everyday communication in webinars and virtual or phone conferences. A modern webpage (www.microbone.de) and a proactive coordinator fostered communication and the networking process. Moreover, our vision and concepts of the µBONE consortium have been published by six PIs in Nature Reviews of Clinical Oncology and several peer-reviewed journals. Of note, several µBONE scientists were promoted to permanent W2/W3 professorships and received prestigious awards as well as ERC grants. This strategy has worked out very well for the first funding period. Therefore, we intend to further promote active communication to ensure an effective networking process between the individual groups and sites within the µBONE consortium. For that purpose, we plan different face-to-face meetings, if possible, and will concurrently strengthen video-assisted communication, too. We will establish professional workshops and training courses to share the expertise in focused areas and plan two smaller workshops and one project academy per year with 10-20 participants from the consortium, including external speakers where applicable. Lab rotations will help to share key technologies in animal models and imaging techniques. In addition, we will promote PhD students by offering expert classes on scientific topics and soft skills and by employing thesis advisory committees. To maximize synergism between basic and translational research, we apply for clinician-scientist positions allocated to individual projects based on documented excellence and track record. To make this consortium attractive for female scientists, we intend to offer specific mentoring programs, a “Flying nanny” childcare service, and flexible bridge funding. Moreover, to sharpen the own cultural perception of each participant and to develop a broader understanding of different perspectives and cultures that may affect science and professional life, we will offer a diversity workshop on intercultural competences. To disseminate our results in addition to scientific publication we will work together with our PR department and plan to produce podcasts and media interviews as well as press releases. These central measures serve the entire consortium and should help to ensure efficient and productive working conditions for all involved scientists.

• DFG Programme: Priority Programmes
• International Connection: Australia

Projects

• Adhesion molecule interactions at the multiple myeloma interface (Applicant Brandl, Andreas )
• Attenuating bone metastases by inhibiting Ror2 signaling and osteoblast senescence (Applicants Hesse, Ph.D., Eric ;  Taipaleenmäki, Ph.D., Hanna )
• Bone marrow stromal cells affect cancer cell homing and growth (Applicant Nakchbandi, Inaam )
• Bone osteotropism: Influence of confinement and mechanical properties of the seeds in the selection of the soil (Applicant Leal-Egana, Aldo )
• Characterization of the impact of bone-seeking tumors on the osteocyte network and the osteocyte-mediated regulation of bone turnover (Applicants Busse, Björn ;  Raum, Kay ;  Rauner, Martina )
• Control of Tumor Cell – Bone Metastasis By Regulation of F-Actin Dynamics (Applicant Jessberger, Rolf )
• Coordination Funds (Applicant Hofbauer, Lorenz C. )
• Deciphering pathogenesis, treatment and reversibility of myeloma bone disease at a single cell resolution (Applicants Merz, Maximilian ;  Weidner, Heike )
• Deciphering the role of CDCP1 for priming the bone metastatic niche in prostate cancer (Applicants Alajati, Ph.D., Abdullah ;  Hölzel, Michael )
• Development and validation of a gene expression assay as prognostic and predictive biomarker in prostate cancer bone metastases (Applicant Sailer, Verena-Wilbeth )
• Dissecting the pleiotropic effects of Dickkopf-1 in homing and colonization of breast cancer cells to and within bone. (Applicants Göbel, Andy ;  Rachner, Tilmann )
• Dissecting the role of ECM-producing stromal cells in bone metastatic progression (Applicant Medyouf, Ph.D., Hind )
• Dissecting the role of extracellular vesicles and their miRNA cargo in prostate cancer. From expression pattern to bone metastasis phenotype. (Applicants Conrad, Stefanie ;  Hofbauer, Lorenz C. )
• Dissecting the role of TAM receptor-ligand interactions in mediating homing and bone colonization by bone seeking cancers (Applicants Ben Batalla, Ph.D., Isabel ;  Loges, Sonja )
• Dissecting the role of TAM receptors in myeloma-induced osteoclast activation and their immune-modulatory function (Applicants Ben Batalla, Ph.D., Isabel ;  Loges, Sonja )
• Dissecting the role/s of breast cancer cell membrane protrusions in invasion, colonization and transformation of the bone marrow microenvironment: From cell biology to clinical applications (Applicants Corbeil, Denis ;  Wimberger, Pauline )
• Functional characterization of bone metastasis-initiating and radioresistant prostate tumor cells (Applicants Baumann, Michael ;  Dubrovska, Anna ;  Krause, Mechthild ;  Peitzsch, Claudia )
• Influence of the skeletal remodeling status on tumor cell dissemination and metastatic outgrowth (Applicants Amling, Michael ;  Schinke, Ph.D., Thorsten )
• Investigating the role of osteocyte steatosis as underlying mechanisms of the impaired osteocyte network due to bone metastasis (Applicants Busse, Björn ;  Rauner, Martina )
• Mechanisms of metastatic outgrowth of spontaneous bone marrow metastases of human prostate cancer cells in vivo (Applicant Lange, Ph.D., Tobias )
• Modelling and targeting bone metastasis formation in prostate cancer (Applicants Guzvic, Ph.D., Miodrag ;  Klein, Christoph )
• Molecular and functional characterization of the normal and malignant plasma cell – bone interface – from single cell mutual interaction analysis to clinical implications in myeloma bone disease and survival (Applicant Ebert, Regina )
• Molecular characterization and targeting of radioresistant prostate cancer stem-like cell populations with bone metastasis-initiating properties (Applicants Dubrovska, Anna ;  Krause, Mechthild ;  Linge, Annett )
• Molecular Characterization of Bone Metastasis Founder Cells in Prostate Cancer (Applicants Guzvic, Ph.D., Miodrag ;  Klein, Christoph )
• Molecular dissection of signaling pathways exerting bone anabolic and anti-tumor effects of physical stimuli in myeloma bone disease (Applicants Ebert, Regina ;  Jundt, Franziska )
• RAI2 as novel suppressor of cancer cell homing and survival in the bone microenvironment (Applicants Pantel, Klaus ;  Wikman-Kocher, Ph.D., Harriet )
• Regulation of Tumor Cell Dormancy in Human Prostate Cancer Bone Metastasis (Applicant Lange, Ph.D., Tobias )
• Role of Dickkopf-1 as a mediator of inflammation in osteotropic cancers (Applicants Göbel, Andy ;  Rachner, Tilmann )
• The impact of hypoxia pathway proteins in bone marrow niche cells during metastasis homing to bone (Applicants Rauner, Martina ;  Wielockx, Ph.D., Ben )
• The impact of myostatin on breast cancer and multiple myeloma bone metastases (Applicant Dankbar, Ph.D., Berno )
• The role of adipocytes in the bone tumor micro-environment (Applicants Bozec, Aline ;  Bäuerle, Tobias )
• The role of TRIM proteins in colonization of the bone and bone microenvironment modulation of metastatic prostate cancer. (Applicant Perner, Sven )
• The role of tumor-associated macrophages in bone metastasis formation in zebrafish (Applicant Knopf, Franziska )
• Unraveling tumor-microenvironmental communication in nascent bone metastasis utilizing zebrafish xenografts (Applicant Engel, Felix B. )

• Spokesperson: Professor Dr. Lorenz C. Hofbauer