Cancer and Bone
Fatal Attraction – Why Bone Cells Home to Bone
Over the course of their lifetime, one out of eight women and men will develop breast or prostate cancer. These tumors display a high tendency to spread to bone, hibernate for several years, and rapidly destroy bone at later stages of bone metastases. Bone metastases due to breast and prostate cancer severely compromise the quality of life and indicate poor outcome. The mechanisms how and why these tumor cells metastasize to bone and the contribution of host factors from the bone microenvironment are still poorly understood.
Our group aims at identifying important bone and tumor factors that cause bone metastasis in breast and prostate cancer. The specific projects include host-derived Wnt5a, the prognostic value of the Wnt inhibitor Dickkopf-1, and the role of the osteocyte network. To accomplish these ambitious aims, our group employs modern cell culture systems, combines preclinical models of bone metastases with high-resolution imaging, and makes use of access to patient material for clinical validation.
We expect that a better knowledge of these principles facilitates individualized therapies in the future.
Martina Rauner, PhD
«Cancer is tricky. Its complexity is overwhelming, yet, it needs to be better understood in order to diagnose it early and treat cancer patients more effectively»
Tilman Rachner, MD
«Be curious! Ask questions! Find out!»
Lorenz Hofbauer, MD
«It takes a motivated team to move ahead.»
Peyman Hadji, Krankenhaus Nordwest, Frankfurt
Sabine Kasimir-Bauer, Universitätsklinikum Essen
Christian Schem, Universitätsklinikum Schleswig-Holstein, Kiel
Pauline Wimberger & PD Jan Kuhlmann, Universitätsklinikum Dresden
Laurie McCauley, University of Michigan, Ann Arbor, USA
Ben Wielockx, Universitätsklinikum Dresden
Rachner TD, Kasimir-Bauer S, Göbel A, Erdmann K, Hoffmann O, Browne A, Wimberger P, Rauner M, Hofbauer LC, Kimmig R, Bittner AK. Prognostic value of RANKL/OPG serum levels and disseminated tumor cells in nonmetastatic breast cancer. Clin Cancer Res. 2019. (in press)
Kresinsky A, Schnöder TM, Jacobsen ID, Rauner M, Hofbauer LC, Ast V, König R, Hoffmann B, Svensson CM, Figge MT, Hilger I, Heidel FH, Böhmer FD, Müller JP. Lack of CD45 in FLT3-ITD mice results in a myeloproliferative phenotype, cortical porosity, and ectopic bone formation. Oncogene. 2019. (in press)
Göbel A, Breining D, Rauner M, Hofbauer LC, Rachner TD. Induction of 3-hydroxy-3-methylglutaryl-CoA reductase mediates statin resistance in breast cancer cells. Cell Death Dis. 2019;10:91.
Thiele S, Zimmer A, Göbel A, Rachner TD, Rother S, Fuessel S, Froehner M, Wirth MP, Muders MH, Baretton GB, Jakob F, Rauner M, Hofbauer LC. Role of WNT5A receptors FZD5 and RYK in prostate cancer cells. Oncotarget. 2018; 9:27293-304.
Browne AJ, Kubasch ML, Göbel A, Hadji P, Chen D, Rauner M, Stölzel F, Hofbauer LC, Rachner TD. Concurrent antitumor and bone-protective effects of everolimus in osteotropic breast cancer. Breast Cancer Res. 2017; 19, 1–15.
Thiele S, Rachner TD, Rauner M, Hofbauer LC. WNT5A and its receptors in the bone-cancer dialogue. J Bone Miner Res. 2016; 31:1488-96.
Göbel A, Thiele S, Browne AJ, Rauner M, Zinna VM, Hofbauer LC, Rachner TD. Combined inhibition of the mevalonate pathway with statins and zoledronic acid potentiates their anti-tumor effects in human breast cancer cells. Cancer Lett. 2016; 375, 162–71.
Browne AJ, Göbel A, Thiele S, Hofbauer LC, Rauner M, Rachner TD. MAPK regulates the Wnt inhibitor Dickkopf-1 in osteotropic prostate cancer cells. Cell Death Dis. 2016; 7, 1–11.
Göbel A, Browne AJ, Thiele S, Rauner M, Hofbauer LC, Rachner TD. Potentiated suppression of Dickkopf-1 in breast cancer by combined administration of the mevalonate pathway inhibitors zoledronic acid and statins. Breast Cancer Res. Treat. 2015; 154:623–31.
Thiele S, Göbel A, Rachner TD, Fuessel S, Froehner M, Muders MH, Baretton GB, Bernhardt R, Jakob F, Glüer CC, Bornhäuser M, Rauner M, Hofbauer LC. WNT5A has anti-prostate cancer effects in vitro and reduces tumor growth in the skeleton in vivo. J Bone Miner Res. 2015; 30:471-80.
Rachner TD, Thiele S, Göbel A, Browne A, Fuessel S, Erdmann K, Wirth MP, Fröhner M, Todenhöfer T, Muders MH, Kieslinger M, Rauner M, Hofbauer LC. High serum levels of Dickkopf-1 are associated with a poor prognosis in prostate cancer patients. BMC Cancer 2014; 14:649.
Hofbauer LC, Rachner TD, Coleman RE, Jakob F. Endocrine aspects of bone metastases. Lancet Diabetes Endocrinol. 2014;2:500-12.