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. Bernhard Homey and Dr. Anja Müller-Homey

 

Dept. of Dermatology
Research Laboratory for Dermato-Immunology and Oncology
University of Düsseldorf
Moorenstrasse 5
D-40225 Düsseldorf, Germany
Phone office: ++49 (0) 211 811 77 75
Phone lab: ++49 (0) 211 811 78 53
Fax: ++49 (0) 211 811 7316


Lab Homepage

homey(at)mail.rz.uni-duesseldorf.de

a.mueller(at)uni-duesseldorf.de

   
 
The chemokine crosstalk at the "tumor-vessel interface"

During tumor progression, malignant cells interact with stromal cells and modulate both hemangio- as well as lymphangiogenesis. Subsequently, intravasation of tumor cells starts a cascade finally leading to survival-limiting metastasis formation. These processes suggest bi-directional communication pathways guiding sprouting microvessels to tumors and instructing tumor cells to intravasate. To date, the underlying chemoattractive signals remain largely unknown. In the present project, we will investigate whether tumor cell-derived chemokines organize lymphangiogenesis and chemokines produced by lymphatic endothelial cells enable tumor cells to invade into lymphatic vessels initiating metastatic dissemination. To address these questions, we will take advantage of the scientific expertise within the SPP1190 consortium and use state of the art imaging tools, tumor models as well unique models of in vitro and in vivo lymphangiogenesis. Within the consortium, we will provide expertise on chemokines and their receptors, qPCR analysis of all known human and mouse chemokines/receptors, human immortalized blood and lymphatic microvascular endothelial cells, CCR6-, CCR8-, CCR9-deficient mice, neutralizing anti-chemokine and anti-chemokine receptor antibodies as well as chemokine receptor antagonists.


Figure 1: Bi-directional communication pathways at the tumor - vessel interface.

 
- Relevant recent publications -

Müller A, Sonkoly E, Eulert C, Gerber PA, Kubitza R, Schirla K, Franken-Kunkel P, Poremba C, Snyderman C, Klotz LO, Ruzicka T, Bier H, Zlotnik A, Whiteside TL, Homey B, Hoffman TK: Chemokine receptors in head and neck cancer: determination of metastatic spread and regulation during chemotherapy. Int J Cancer 118: 2147-57, 2006.

Nestle FO, Conrad C, Tun-Kyi A, Homey B, Boyman O, Burg G, Liu YJ, Gilliet M: Plasmacytoid dendritic cells (PDC) initiate psoriasis through IFN-alpha production. J Exp Med 202: 135-43, 2005.

Gombert M, Dieu-Nosjean MC, Winterberg F, Bünemann E, Kubitza RC, Da Cunha L, Haahtela A, Lehtimäki S, Müller A, Rieker J, Meller S, Pivarcsi A, Koreck A, Fridman WH, Zentgraf HW, Pavenstädt H, Amara A, Caux C, Kemeny L, Alenius H, Lauerma A, Ruzicka T, Zlotnik A, Homey B: CCL1-CCR8 Interactions: An axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation. J Immunol 174: 5082-91, 2005.

Vanbervliet B, Bendriss-Vermare N, Massacrier C, Homey B, de Bouteiller O, Briere F, Trinchieri G, Caux C: The inducible CXCR3 ligands control plasmacytoid dendritic cell responsiveness to the constitutive chemokine stromal cell-derived factor 1 (SDF-1)/CXCL12. J Exp Med 198: 823-30, 2003.

Homey B, Müller A, Zlotnik A: Chemokines: agents for the immunotherapy of cancer? Nature Rev Immunol 2:175-84, 2002.

Homey B, Alenius H, Müller A, Soto H, Bowman EP, Yuan W, McEvoy L, Lauerma AI, Assmann T, Bunemann E, Lehto M, Wolff H, Yen D, Marxhausen H, To W, Sedgwick J, Ruzicka T, Lehmann P, Zlotnik A: CCL27-CCR10 interactions regulate T cell-mediated skin inflammation. Nat Med 8:157-65, 2002.

Müller A*, Homey B*, Soto H, Ge N, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verástegui E, Zlotnik A:. Involvement of chemokine receptors in breast cancer metastasis. (*equal contribution) Nature 410: 50-56, 2001.

 

 
 
 
 
 
 

 

 
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Impressum | Last update: 06/26/2008