associated project

/project 4

Category: .projects
A. Trauzold and H. Kalthoff, Kiel

Impact of inflammatory mechanisms on osteoblast-metastatic tumor cell interaction

The impact of pro-inflammatory cytokines in bone metastases of breast cancer cells has not yet been deeply studied in its complexity and interdependency. Recently, we discovered that the nuclear death receptors TRAIL-R1/-R2 regulate microRNA processing and epithelial-mesenchymal transition (EMT). In our project we will test the hypotheses I) that inflammatory cytokines contribute to EMT in osteotropic tumor cells, and II) that TRAIL-R1/2-mediated mechanisms of EMT induction stimulate bone metastases.


PD Dr. rer. nat. Anna Trauzold
Division of Molecular Oncology, Institute for Experimental Cancer Research, Comprehensive Cancer Center - North, Kiel
Research focus: inflammation and cancer, apoptosis-resistance mechanisms, non-apoptotic and apoptotic functions of death receptors (TRAIL-Rs, CD95, TNF-R1)

Prof. Dr. rer. nat. Holger Kalthoff
Division of Molecular Oncology, Institute for Experimental Cancer Research, Comprehensive Cancer Center - North, Kiel
Research focus: molecular resistance mechanisms of epithelial tumor cells, non-apoptotic (pro-inflammatory) mechanisms of death receptors, Immunosuppression in pancreatic cancer, clinically adapted murine tumor models and molecular imaging, detection and characterization of disseminated tumor cells

Project-related list of publications
Voigt S, Philipp S, Davarnia P, Winoto-Morbach S, Röder C, Arenz C, Trauzold A, Kabelitz D, Schütze S, Kalthoff H, Adam D. TRAIL-induced programmed necrosis as a novel approach to eliminate tumor cells. BMC Cancer 2014;14:74.
Haselmann V, Kurz A, Bertsch U, Hübner S, Olempska-Müller M, Fritsch J, Häsler R, Pickl A, Fritsche H, Annewanter F, Engler C, Fleig B, Bernt A, Röder C, Schmidt H, Gelhaus C, Hauser C, Egberts JH, Heneweer C, Rohde AM, Böger C, Knippschild U, Röcken C, Adam D, Walczak H, Schütze S, Janssen O, Wulczyn FG, Wajant H, Kalthoff H, Trauzold A. Nuclear death receptor TRAIL-R2 inhibits maturation of let-7 and promotes proliferation of pancreatic and other tumor cells. Gastroenterology 2014;146:278-90. 
Schem C, Bauerschlag D, Bender S, Lorenzen AC, Hamann S, Rösel F, Kalthoff H, Glüer CC, Jonat W, Tiwari S. Preclinical evaluation of an antiangiogenesis inhibitor as a single agent and in combination with zoledronic acid in a mouse model of bone metastases. BMC Cancer 2013;24;13:32. 
Hirner H, Günes C, Bischof J, Wolff S, Grothey A, Kühl M, Oswald F, Wegwitz F, Bösl MR, Trauzold A, Henne-Bruns D, Peifer C, Leithäuser F, Deppert W, Knippschild U. Impaired CK1 delta activity attenuates SV40-induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo. PLoS One 2012;7:29709.
Tiwari S, Schem C, Lorenzen AC, Kayser O, Wiese C, Graeff C, Peña J, Marshall RP, Heller M, Kalthoff H, Jonat W, Glüer CC. Application of ex vivo micro-computed tomography for assessment of in vivo fluorescence and plain radiographic imaging for monitoring bone metastases and osteolytic lesions. J Bone Miner Metab 2012;30:373-80. 

Zhou DH, Yang LN, Roder C, Kalthoff H, Trauzold A. TRAIL-induced expression of uPA and IL-8 strongly enhanced by overexpression of TRAF2 and Bcl-xL in pancreatic ductal adenocarcinoma cells. Hepatobiliary Pancreat Dis Int 2013;12:94-8.

Tiwari S, Egberts JH, Korniienko O, Köhler L, Trauzold A, Glüer CC, Kalthoff H. Assessment of anti-inflammatory tumor treatment efficacy by longitudinal monitoring employing sonographic micro morphology in a preclinical mouse model. BMC Med Imaging.2011;11:15.

Roos C, Wicovsky A, Müller N, Salzmann S, Rosenthal T, Kalthoff H, Trauzold A, Kürbitz C, Heise D, Redmer T, Goumas F, Arlt A, Lemke J, Rimbach G, Kalthoff H, Trauzold A. Epicatechin gallate and catechin gallate are superior to epigallocatechin gallate in growth suppression and anti-inflammatory activities in pancreatic tumor cells. Cancer Sci 2011;102:728-34.

Röder C, Trauzold A, Kalthoff H. Impact of death receptor signaling on the malignancy of pancreatic ductal adenocarcinoma. Eur J Cell Biol 2011;90:450-5.

Ehrenschwender M, Siegmund D, Wicovsky A, Kracht M, Dittrich-Breiholz O, Spindler V, Waschke J, Kalthoff H, Trauzold A, Wajant H. Mutant PIK3CA licenses TRAIL and CD95L to induce non-apoptotic caspase-8-mediated ROCK activation. Cell Death Differ 2010;17:1435-47.

Seher A, Henkler F, Kneitz C, Wajant H. Soluble and transmembrane TNF-like weak inducer of apoptosis differentially activate the classical and noncanonical NF-kappa B pathway. J Immunol 2010;185:1593-605.

Lemke J, Noack A, Adam D, Tchikov V, Bertsch U, Röder C, Schütze S, Wajant H, Kalthoff H,  Trauzold A.  TRAIL signaling is mediated by DR4 in pancreatic tumor cells despite the expression of functional DR5. J Mol Med 2010;88:729-740.

von Forstner C, Egberts JH, Ammerpohl O, Niedzielska D, Buchert R, Mikecz P, Schumacher U, Peldschus K, Adam G, Pilarsky C, Grutzmann R, Kalthoff H, Henze E, Brenner W. Gene expression patterns and tumor uptake of 18F-FDG, 18F-FLT, and 18F-FEC in PET/MRI of an orthotopic mouse xenotransplantation model of pancreatic cancer. J Nucl Med 2008;49:1362-1370.

Egberts JH, Cloosters V, Noack A, Schniewind B, Thon L, Klose S, Kettler B, von Forstner C, Kneitz C, Tepel J, Adam D, Wajant H,  Kalthoff H,  Trauzold A. Anti-tumor necrosis factor therapy inhibits pancreatic tumor growth and metastasis. Cancer Res 2008;68:1443-1450.

Egberts JH, Schniewind B, Pätzold M, Kettler B, Tepel J,  Kalthoff H,  Trauzold A. Dexamethasone reduces tumor recurrence and metastasis after pancreatic tumor resection in SCID mice. Cancer Biol Ther 2008;7:1044-1050.

Siegmund D, Klose S, Zhou D, Baumann B, Röder C, Kalthoff H, Wajant H, Trauzold A. Role of caspases in CD95L- and TRAIL-induced non-apoptotic signalling in pancreatic tumour cells. Cell Signal 2007;19:1172-1184.

Trauzold A, Siegmund D, Schniewind B, Sipos B, Egberts J, Zorenkov D, Emme D, Röder C, Kalthoff H*, Wajant H. TRAIL promotes metastasis of human pancreatic ductal adenocarcinoma. Oncogene 2006;25:7434-7439. 

Trauzold A, Roder C, Sipos B, Karsten K, Arlt A, Jiang P, Martin-Subero JI, Siegmund D, Muerkoster S, Pagerols-Raluy L, Siebert R, Wajant H, Kalthoff H. CD95 and TRAF2 promote invasiveness of pancreatic cancer cells. FASEB J 2005;19:620-622.

Kremer M, Quintanilla-Martinez L, Fuchs M, Gamboa-Dominguez A, Haye S,  Kalthoff H, Rosivatz E, Hermannstädter C, Busch R, Höfler H, Luber B. Influence of tumor-associated E-cadherin mutations on tumorigenicity and metastasis. Carcinogenesis 2003;24:1879-1886.

Trauzold A, Wermann H, Arlt A, Schutze S, Schafer S, Oestern S, Roder C, Ungefroren H, Lampe E, Heinrich M, Walczak H, Kalthoff H. CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-κB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells. Oncogene 2001;20:4258-4269.

Technische Universitt Dresden    Christian-Albrechts-Universitt zu Kiel    Julius-Maximilians-Universitt Wrzburg
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