Christoph Peters

Institution: Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität Freiburg

Address:

Zentrum für Biochemie und Molekulare Zellforschung (ZBMZ) Albert-Ludwigs-Universität Freiburg Stefan-Meier-Straße 17 D-79104 Freiburg

Email: christoph.peters@mol-med.uni-freiburg.de

Group website: www.mol-med.uni-freiburg.de

Phone: +49 761 203 9600/ 9601

Research interests:

Cancer Invasion and Metastasis Coordinator of the Collaborative Research Center 850 "Control of Cell Motility in Morphogenesis, Cancer Invasion and Metastasis" Project B7 – Impact of Cancer- and Stroma-Cell Derived Endosomal/Lysosomal Proteases on Invasion and Metastasis of Mammary Cancer (Reinheckel, Peters) Proteolysis is a hallmark process during invasion and metastasis of solid cancers. The expression of the cysteine-type proteases cathepsin B and cathepsin X are correlated to poor prognosis of cancer patients and genetic deficiency of these enzymes in cancer mice results in reduced tumor and metastatic burden. However, causal insights into the in vivo functions of cathepsins B and X in tumor progression are still missing. We will identify the cell types and the molecular networks in which cathepsins B and X are critical for cancer cell invasion and metastasis in a mouse model of breast cancer. BIOSS Centre for Biological Signalling Studies From Analysis to Synthesis BIOSS Area B: Supra-cellular Signalling Pathways BIOSS During development, growth, and regeneration, complex signalling environments recruit cells from stem cell pools, direct their differentiation paths, and organise them in 3D into specialized organ structures. Research in BIOSS-B focuses on molecular nature, organization, and logic of these signalling systems. Microenvironment remodeling by the degradome of breast cancer stem cells (link) PD Dr. Thomas Reinheckel, Prof. Dr. Christoph Peters, Dr. Oliver Schilling (Institute of Molecular Medicine and Cell Research) Carcinomas contain cell populations with stem cell properties that are critical for tumor growth, tumor spread, and colonization of distant sites. Proteolysis is a hallmark feature of invasive growth and metastasis – thus we aim to functionally characterize the degradome, i.e. the complement of proteases and their endogenous protease inhibitors, of cancer stem cells in its ability to remodel the microenvironment of those cells. To this end, the processing of ECM proteins by surface-bound or secreted proteases of stem cells and the functional implication of these cleavage events will be studied in stem cell culture and in vivo by orthotopic transplantation of cancer stem cells with genetic or pharmacologic perturbation of the protease network. Identification of kinases driving the metastatic behaviour of breast cancer(link) Dr. Tilman Brummer, Prof. Thomas Reinheckel, Prof. Christoph Peters (Institute for Molecular Medicine and Cell Research) Tumour progression is not only caused by dysregulated intracellular signalling, but also by altered interaction of cells with their environment. Importantly, these processes are connected to each other as alterations of signaling and metabolic pathways caused by oncogenic events within the tumour cell contribute to the establishment and dynamic remodelling of the tumor microenvironment, e.g. by inducing proteolytic activities and secreting signaling molecules that address stromal, endothelial and immune cells. Indeed, the tumour microenvironment has drastic effects on the establishment and progression of a tumour. For example, depending on the tumour microenvironment, the immune system can either suppress or promote tumour development. In this project, we want to combine our expertise in 3D cell cultures and material engineering to obtain novel insights by re-building the tumour microenvironment in a well-defined experimental setting that also allows its multi-parameter monitoring in real time.

Selected publications:

1. Bengsch F, Buck A, Günther SC, Seiz JR, Tacke M, Pfeifer D, von Elverfeldt D, Sevenich L, Hillebrand LE, Kern U, Sameni M, Peters C, Sloane BF, Reinheckel T. Cell type-dependent pathogenic functions of overexpressed human cathepsin B in murine breast cancer progression. Oncogene. 2014 Sep 4;33(36):4474-84. doi: 10.1038/onc.2013.395. Epub 2013 Sep 30. Pubmed24077280 2. Butinar M, Prebanda MT, Rajković J, Jerič B, Stoka V, Peters C, Reinheckel T, Krüger A, Turk V, Turk B, Vasiljeva O. Stefin B deficiency reduces tumor growth via sensitization of tumor cells to oxidative stress in a breast cancer model.Oncogene. 2014 Jun 26;33(26):3392-400. doi: 10.1038/onc.2013.314. Epub 2013 Aug 19. Pubmed23955077 3. Mikhaylov G, Mikac U, Magaeva AA, Itin VI, Naiden EP, Psakhye I, Babes L, Reinheckel T, Peters C, Zeiser R, Bogyo M, Turk V, Psakhye SG, Turk B, Vasiljeva O. Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment. Nat Nanotechnol. 2011 Aug 7;6(9):594-602.doi:10.1038/nnano. 2011.112. PubMed21822252 4. Sevenich L, Werner F, Gajda M, Schurigt U, Sieber C, Müller S, Follo M, Peters C, Reinheckel T. Transgenic expression of human cathepsin B promotes progression and metastasis of polyoma-middle-T-induced breast cancer in mice. Oncogene. 2011 Jan 6;30(1):54-64. PubMed20818432. 5. Sevenich L, Schurigt U, Sachse K, Gajda M, Werner F, Müller S, Vasiljeva O, Schwinde A, Klemm N, Deussing J, Peters C, Reinheckel T. Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2497-502. Pubmed20133781 6. Vasiljeva O, Korovin M, Gajda M, Brodoefel H, Bojic L, Krüger A, Schurigt U, Sevenich L, Turk B, Peters C, Reinheckel T. Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice. Oncogene. 2008 Jul 10;27(30):4191-9. Pubmed18345026 7. Vasiljeva O, Papazoglou A, Kruger A, Brodoefel H, Korovin M, Deussing J, Augustin N, Nielsen BS, Almholt K, Bogyo M, Peters C, Reinheckel T. Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Res. 2006 May 15;66(10):5242-50. Pubmed16707449 8. Gocheva V, Zeng W, Ke D, Klimstra D, Reinheckel T, Peters C, Hanahan D, Joyce JA. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev. 2006 Mar 1;20(5):543-56. Pubmed16481467

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