Priority Research Program of the German Research Foundation (DFG)
SPP 1190 - THE TUMOR - VESSEL INTERFACE

SPP 1190 - Projects
 
A. Abdollahi / P. Huber/
J. Debus

A. Acker-Palmer
T. Acker
R. Adams
F. Alves
H. Augustin
H. Beck / M. Conrad
G. Breier / B. Wielockx
P. Friedl
C. Bruns / P. Nelson
B. Homey / A. Müller-Homey
Ch. Klein
V. Orian-Rousseau / H. Ponta
K.T. Preissner
B. Sipos
J. Sleeman
P. Vajkoczy
 

 

Prof. Dr. Bence Sipos

 

Department of Pathology
Institut für Allgemeine Pathologie
Universitätsklinikum Tübingen
Liebermeisterstraße 8
D-72076 Tübingen
Phone: ++49 (0) 7071-29 80 215
Fax: ++49 (0) 7071-29 29 91

Lab Homepage

Bence.Sipos(at)med.uni-tuebingen.de

 

 
The role of the chemokine/chemokine receptor system in tumor progression of pancreatic ductal carcinoma
The mechanism by which tumor cells invade lymphatic vessels is unknown. Based on our previous studies and preliminary results we hypothesize that pancreatic adenocarcinoma, which represents one of the most aggressive malignancies and shows a high rate of lymph node metastasis without functionally relevant lymphangiogenesis, may exploit a regulatory mechanism that controls the fate and route of white blood cells from organs to lymph nodes via lymphatic vessels. This process is mediated by chemokines which are expressed in lymphatics, attracting and directing chemokine receptor bearing cells. Our main goal is (i) to define the significance of chemokine receptors expressed in pancreatic adenocarcinoma for invasion into lymph vessels and for metastasis to lymph nodes (ii) to define the basal chemokine expression of lymphatic endothelial cells and how it is modulated by interaction with pancreatic adenocarcinoma cells, (iii) to define the alterations in the chemokine expression in lymph vessels due to peritumoral chronic inflammation and its effect on the metastatic capacity of pancreatic carcinomas.
 
- Relevant recent publications -

Grützmann R, Foerder M, Alldinger I, Staub E, Brümmendorf T, Röpke S, Li X, Kristiansen G, Jesnowski R, Sipos B, Löhr M, Lüttges J, Ockert D, Klöppel G, Saeger HD, Pilarsky C: Gene expression profiles of microdissected pancreatic ductal adenocarcinoma. Virchows Arch 443: 508-517, 2003.

Schreiner B, Baur DM, Fingerle AA, Zechner U, Greten FR, Adler G, Sipos B, Klöppel G, Hameister H, Schmid RM: Pattern of secondary genomic changes in pancreatic tumors of Tgf-alpha / Trp53+/- transgenic mice. Genes Chromos Cancer 38: 240-248, 2003.

Sipos B, Möser S, Kalthoff H, Török V, Löhr M, Klöppel G: A comprehensive characterization of pancreatic ductal carcinoma cell lines: towards the establishment of an in vitro research platform. Virchows Arch 442: 444-452, 2003.

Trauzold A, Schmiedel S, Sipos B, Wermann H, Westphal S, Röder C, Klapper W, Arlt A, Lehnert L, Ungefroren H, Johannes F-J, Kalthoff H: PKCmu prevents CD95-mediated apoptosis and enhances proliferation in pancreatic tumour cells. Oncogene 22: 8939-8947, 2003.

Bando H, Brokelmann M, Toi M, Alitalo K, Sleeman JP, Sipos B, Grone HJ, Weich HA: Immunodetection and quantification of vascular endothelial growth factor receptor-3 in human malignant tumor tissues. Int J Cancer 111: 184-191, 2004.

Grützmann R, Pilarsky C, Ammerpohl O, Lüttges J, Böhme A, Sipos B, Foerder M, Alldinger I, Jahnke B, Schackert HK, Kalthoff H, Kremer B, Klöppel G, Saeger HD: Gene expression profiling of microdissected pancreatic ductal carcinomas using hogh-density DNA microarrays. Neoplasia 6: 611-622, 2004.

Müerköster S, Wegehenkel K, Arlt A, Witt M, Sipos B, Kruse M-L, Sebens T, Klöppel G, Kalthoff H, Fölsch UR, Schäfer H: Tumor stroma interactions induce chemoresistance in pancreatic ductal carcinoma cells involving increased secretion and paracrine effects of nitric oxide and interleukin-1b. Cancer Res 64: 1331-1337, 2004.

Sipos B, Klapper W, Kruse M-L, Kalthoff H, Kerjaschki D, Klöppel G: Expression of lymphangiogenic factors and evidence of intratumoral lymphangiogenesis in pancreatic endocrine tumors. Am J Pathol 165: 1187-1197, 2004.

Sipos B, Hahn D, Carceller A, Piulats J, Hedderich J, Kalthoff H, Goodman SL, Kosmahl M, Klöppel G: Immunohistochemical screening for b6-integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up-regulation in pancreatic ductal adenocarcinomas in vivo and in vitro. Histopathology 45: 226-236, 2004.

Weich HA, Bando H, Brokelmann M, Baumann P, Toi M, Barleon B, Alitalo K, Sipos B, Sleeman J: Quantification of vascular endothelial growth factor-C (VEGF-C) by a novel ELISA. J Immunol Methods 285: 145-155, 2004.

Müerköster S, Arlt A, Sipos B, Witt M, Großman M, Klöppel G, Kalthoff H, Fölsch UR, Schäfer H: Increased expression of the E3-ubiquitin ligase receptor subunit bTRCP1 relates to constitutive nuclear factor-kB activation and chemoresistance in pancreatic carcinoma cells. Cancer Res 65: 1316-1324, 2005.

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

Sipos B, Kojima M, Tiemann K, Klapper W, Kruse M-L, Kalthoff H, Schniewind B, Tepel J, Weich H, Kerjaschki D, Klöppel G: Lymphatic spread of ductal pancreatic adenocarcinoma is independent of lymphangiogenesis. J Pathol 207: 301-312, 2005.

Tepel J, Dagvadorj O, Kapischke M, Sipos B, Leins A, Kremer B , Kalthoff H: Significant growth inhibition of orthotopic pancreatic ductal adenocarcinoma by CpG oligonucleotides in immunodeficient mice. Int J Colorectal Dis 21: 365-372, 2005.

Book chapter

Sipos B, Real FX, Moore P, Kalthoff H, Scarpa A, Klöppel G: Genetic and cellular characteristics of pancreatic carcinoma cell lines. In: Gress TM, Neoptolemos JP, Lemoine NR, Real FX (eds.) Exocrine pancreas cancer. The European Pancreatic Cancer-Research Cooperative (EPC-RC). Felsenstein CCCP, Hannover, pp 120-135, 2005

 

 
 
 
 
 
 

 

 
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Impressum | Last update: 06/22/2009