Tumor microenvironment in cancer biology and targeting
Background
Carcinoma progression is accompanied by reorganization of the connective tissue compartment leading to a specialised tumor microenvironment (TME). TME includes activation of local fibroblasts, recruitment and activation of inflammatory cells, reorganization of the extracellular matrix and tumor angiogenesis. Cross-talk of tumor and stroma cells is crucial for tumor growth, invasion and metastasis and affects drug sensitivity.
The expertise and research activities of JUH groups working on different aspects of TME are focused on
- mechanisms of epigenetic regulation of tumor cell behaviour by stroma cells and
- regulation of tumor angiogensis.
Coordinators
Interdisciplinary research areas click here
Project drafts for UTC collaborations
PI |
Projects - short titles |
Markert |
microRNA profiles and function in trophoblastic cells |
Berndt, Liebmann |
Regulation of activated fibroblasts by EGFR inhibition (Gefitinib) |
Friedrich, Junker, Berndt |
Cell-specific signaling in tumor cell - fibroblast interactions |
Kaufmann, Berndt |
Hepatic stellate cells, hepatic carcinoma cells and EGFR inhibition |
Berndt, Heller, Junker, Kaufmann |
HUVEC sensitivity against sunitinib/sorafenib - role of fibroblasts |
Wagner, Clement, Hochhaus |
Circulating endothelial cells and circulating endothelial progenitor cells |
Heller, Böhmer |
Tumor cell-mediated inactivation of PTPs and angiogenesis |
Hilger |
Multispectral imaging of tumor metabolism and vascularisation |
Junker, Heller |
Mechanisms of antiangiogenic therapy resistance in RCC |
Kaufmann, Heller |
Relevance of PAR2 signaling in endothelial cells for HCC progression |
Markert, Fitzgerald, Weise |
Trophoblast-endothelial cell interaction as model for tumor angiogenesis |
Wartenberg |
Role of ROS.generation of leukocytes in tumor angiogenesis |
Current funding and expertise
- tight interaction of different groups of the University Hospital Jena and local, regional and international collaborations
- Accepted or submitted grants related to the TME topic: 2 EC, 8 DFG, 4 BMBF, 2 Deutsche Krebshilfe
- Well developed background of lab infrastructure, methods, and models for investigation of TME
Expertise (I)
- biology of tumor invasion at pathohistological level
- invasion associated matrix remodelling - role of fibroblasts
- models for activated fibroblasts
- tumor cell - fibroblast interaction models for OSCC, RCC, HCC, UBC
- analyses of epigenetic regulation
- Xenograft models for OSCC, RCC, UBC and HCC
- biochemistry of EGFR signaling
Expertise (II)
- tumor cells (RCC, HCC) / endothelial cells / stroma cells
- co-culture models of tumor or stroma cells with endothelial cells
- vascular extracellular matrix remodelling
- angiogenic signaling and angiogenesis assays
- circulating endothelial cells
- in vivo imaging of tumor vascularisation
- Xenograft tumor models
Publications
- Stahmann N, A. Woods, K. Spengler, A. Heslegrave, S. Krause, B. Viollet, D. Carling, R. Heller: AMP-activated protein kinase activation by vascular endothelial growth factor mediates endothelial angiogenesis independent of NO synthase activation. J. Biol. Chem. 285, 10638-10652, 2010.
- Hannig M, Figulla HR, Sauer H, Wartenberg M. Control of leucocyte differentiation from embryonic stem cells upon vasculogenesis and confrontation with tumour tissue. J Cell Mol Med. 2010 Jan;14(1-2):303-12.
- Kaufmann R, Oettel C, Horn, A., Halbhuber, K.-J., Eitner, A., Krieg, R., Katenkamp, K., Henklein, P., Westermann, M., Böhmer, F.D., Ramachandran, R., Saifeddine, M., Hollenberg, M.D., Settmacher, U. C-Met receptor tyrosine kinase transactivation is involved in proteinase-activated receptor 2-mediated hepatocellular carcinoma cell invasion. Carcinogenesis 30:1487-1496 (2009).
- Busch S, Renaud SJ, Schleussner E, Graham C, Markert UR. mTOR mediates human trophoblast invasion through regulation of matrix-remodeling enzymes and is associated with serine phosphorylation of STAT3. Exp Cell Res 2009; 315:1724-33.
- Berndt A, Kollner R, Richter P, Franz M, Voigt A, Borsi L, Giavazzi R, Neri D, Kosmehl H. A comparative analysis of oncofetal fibronectin and tenascin-C incorporation in tumour vessels using human recombinant SIP format antibodies. Histochem Cell Biol 2010, 133:467-475