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English Intern
    Lehrstuhl für Orthopädie

    DFG SPP µBone

    The German Research Society (DFG) started a new Priority Program entitled "µBONE - Colonisation and Interactions of Tumor Cells within the Bone Microenvironment" (SPP 2084). Würzburg University participates in this Research Program with 2 projects of the Department of Internal Medicine II (Prof. Andreas Beilhack Research Group) and the Orthopedic Department (see project below). This project is run in close cooperation with the Department for functional materials in medicine and dentistry of Würzburg University. Within µBone several groups are dealing with breast and prostate cancer metastases to bone
    while a subgroup - including the 2 Würzburg projects - is working on the interaction of
    Multiple Myeloma with the Bone Microenvironment.

    Project Title
    Molecular and functional characterization of the normal and malignant plasma cell : bone interface
    – from single cell mutual interaction to clinical implications in angiogenesis,
    bone disease and survival

    Principal Investigators
    Franz Jakob / Regina Ebert and Dirk Hose / Anja Seckinger
    Orthopedic Department Wuerzburg University and Department of Internal Medicine V University of Heidelberg

    Background
    Myeloma cells interact with skeletal precursors and confer osteolysis and inhibition of bone regeneration. Building on previous complemen-tary and synergistic experience of our groups and network, dissecting this molecular crosstalk will reveal targets to identify, mobilize and kill niche-protected dormant myeloma cells in order to cure residual disease and reconstitute bone regeneration

    Objectives

    • Molecular and functional characterization of the bone marrow niche of normal vs. malignant plasma cells
    • Relate niche constitution and interaction factors to large cohort of patient’s malignant plasma cells and comparator populations characterized by molecular profiling and whole-body imaging
    • Functionally validate findings in vitro (CRISPR/CAS9, adherence assays) as well as in vivo (U266-myeloma mouse model)
    • Contribute to a collaborative network within and beyond µBone regarding myeloma dissemination, bone disease and angiogenesis


    Experimental Setup

     

    Publications

    • Solimando AG, Brandl A, Mattenheimer K, Graf C, Ritz M, Ruckdeschel A, Stühmer T, Mokhtari Z, Rudelius M, Dotterweich J, Bittrich M, Desantis V, Ebert R, Trerotoli P, Frassanito MA, Rosenwald A, Vacca A, Einsele H, Jakob F, Beilhack A. JAM-A as a prognostic factor and new therapeutic target in multiple myeloma. Leukemia. 2018 Mar;32(3):736-743. doi: 10.1038/leu.2017.287. Epub 2017 Sep 28.
    • Dotterweich J, Schlegelmilch K, Keller A, Geyer B, Schneider D, Zeck S, Tower RJ, Ebert R, Jakob F, Schütze N. Contact of myeloma cells induces a characteristic transcriptome signature in skeletal precursor cells -Implications for myeloma bone disease. Bone. 2016 Dec;93:155-166. doi: 10.1016/j.bone.2016.08.006. Epub 2016 Aug 9.
    • Dotterweich J, Tower RJ, Brandl A, Müller M, Hofbauer LC, Beilhack A, Ebert R, Glüer CC, Tiwari S, Schütze N, Jakob F. The KISS1 Receptor as an In Vivo Microenvironment Imaging Biomarker of Multiple Myeloma Bone Disease. PLoS One. 2016 May 9;11(5):e0155087. doi: 10.1371/journal.pone.0155087. eCollection 2016.
    • Seckinger A, Meissner T, Moreaux J, Depeweg D, Hillengass J, Hose K, Rème T, Rösen-Wolff A, Jauch A, Schnettler R, Ewerbeck V, Goldschmidt H, Klein B, Hose D. Clinical and prognostic role of annexin A2 in multiple myeloma. Blood. 2012 Aug 2;120(5):1087-94. doi: 10.1182/blood-2012-03-415588. Epub 2012 Jun 15.
    • Neben K, Jauch A, Hielscher T, Hillengass J, Lehners N, Seckinger A, Granzow M, Raab MS, Ho AD, Goldschmidt H, Hose D. Progression in smoldering myeloma is independently determined by the chromosomal abnormalities del(17p), t(4;14), gain 1q, hyperdiploidy, and tumor load. J Clin Oncol. 2013 Dec 1;31(34):4325-32. doi: 10.1200/JCO.2012.48.4923. Epub 2013 Oct 21.
    • Seckinger A, Delgado JA, Moser S, Moreno L, Neuber B, Grab A, Lipp S, Merino J, Prosper F, Emde M, Delon C, Latzko M, Gianotti R, Lüoend R, Murr R, Hosse RJ, Harnisch LJ, Bacac M, Fauti T, Klein C, Zabaleta A, Hillengass J, Cavalcanti-Adam EA, Ho AD, Hundemer M, San Miguel JF, Strein K, Umaña P, Hose D, Paiva B, Vu MD. Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment. Cancer Cell. 2017 Mar 13;31(3):396-410. doi: 10.1016/j.ccell.2017.02.002. Epub 2017 Mar 2.

     

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