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. Georg Breier and Dr. Ben Wielockx
Prof. Dr. Georg Breier

Institute of Pathology
Technical University of Dresden
Carl-Gustav-Carus University
Fetscherstr. 74
D-01307 Dresden, Germany
Tel: ++49 (0) 351-458-5278
Fax: ++49 (0) 351-458-4328

Lab Homepage

Georg.Breier(at)uniklinikum-dresden.de

 

Dr. Ben Wielockx

Emmy Noether group leader (DFG)
Inst. of Pathology -
University of Technology Dresden
Schubertstrasse 15
D-01307 Dresden, Germany
Tel: ++49 (0) 351-458-3038 /3005
Fax: ++49 (0) 351-458-4328

Lab Homepage

Ben.Wielockx(at)uniklinikum-dresden.de

 
The role of HIF prolyl hydroxylases in tumor progression and metastasis
Hypoxia is a major driving force for tumor vascularization and progression. In mammalian cells, the transcriptional complex, hypoxia-inducuble factor (HIF), has emerged as a key regulator of physiological and pathological processes, mediating both local and systemic responses to hypoxia. HIF activity and stability, in turn, is tightly controlled through the enzymatic activity of hydroxylases which serve as cellular oxygen sensors. While the function of HIF in activating the angiogenic program in tumor cells is well established, little is known about the role of hypoxia signalling in endothelial cells. Recent evidence suggests that HIF activity in endothelial cells is critical for angiogenesis and tumor progression. In this project, therefore, we want to focus on the influence of endothelial HIF hydroxylases on the vascularization, growth and metastasis of experimental tumors in mice. These studies will eventually lead to a better understanding of the interplay between tumor cells and the vasculature and may therefore be helpful in the development of new therapies.
 
- Relevant recent publications -

Licht AH, Muller-Holtkamp F, Flamme I, Breier G: Inhibition of hypoxia-inducible factor activity in endothelial cells disrupts embryonic cardiovascular development. Blood 107: 584-90, 2006

Mitola S, Brenchio B, Piccinini M, Tertoolen L, Zammataro L, Breier G, Rinaudo MT, den Hertog J, Arese M, Bussolino F: Type I Collagen limits VEGFR-2 signaling by a SHP2 protein-tyrosine phosphatase-dependent mechanism. Circ Res 98: 45-54, 2006

Rajashekhar G, Willuweit A, Patterson CE, Sun P, Hilbig A, Breier G, Helisch A, Clauss M: Continuous endothelial cell activation increases angiogenesis: evidence for the direct role of endothelium linking angiogenesis and inflammation. J Vasc Res 43: 193-204, 2006

Breier G: Lymphangiogenesis in regenerating tissue: is VEGF-C sufficient? Circ Res 96: 1132-34, 2005

Lai Y, Schneider D, Kidszun A, Hauck-Schmalenberger I, Breier G, Branshorst D, Branshorst H, Iken M, Brendel MD, Bretzel RG, Linn T: Vascular endothelial growth factor increases functional beta-cell mass by improvement of angiogenesis of isolated human and murine pancreatic islets. Transplantation 79: 1530-36, 2005

Masson V, Rodriguez de la Ballina L, Munaut C, Wielockx B, Jost M, Maillard C, Blacher S, Bajou K, Itoh T, Werb Z, Libert C, Foidart J-M and Noël A: Impaired malignant keratinocyte invasion and tumoral vascularization in double MMP2 and MMP9 knock out mice. FASEB J 19: 234-36, 2005

Van Lint P, Wielockx B, Lopez-Otin C, Noel A, and Libert C: MMP8-deficiency leads to reduced development of hepatitis due to reduced LIX cleavage. J Immunol 175: 7642-49, 2005

Wullaert A, Wielockx B, Van Huffel S, Bogaert V, De Geest B, Papeleu P, El Bakkouri K, Heyninck K, Libert C, and Beyaert R: Adenoviral gene transfer of ABIN-1 protects mice from TNF/Galactosamine-induced acute liver failure and lethality. Hepatology 42: 381-89, 2005

Clauss M, Breier G, eds.: "Mechanisms of Angiogenesis". Birkhäuser Verlag Basel, 2004

Hammes HP, Lin J, Wagner P, Feng Y, vom Hagen F, Krzizok T, Renner O, Breier G, Brownlee M, Deutsch U: Angiopoietin-2 causes pericyte dropout in the normal retina. Evidence for involvement in diabetic retinopathy. Diabetes 53: 1104-10, 2004

Heidenreich R, Machein M, Nicolaus A, Hilbig A, Wild C, Clauss M, Plate KH, Breier G: Inhibition of solid tumor growth by gene transfer of dominant-negative VEGF receptor-1 mutants. Int J Cancer 111: 348-57, 2004

Licht AH, Hofmann U, Raab S, Breier G: Endothelium-specific Cre recombinase activity in flk-1-Cre transgenic mice. Dev Dyn 229: 312-18, 2004

Raab S, Beck H, Gaumann A, Yuce A, Gerber HP, Plate KH, Hammes HP, Ferrara N, Breier G: Impaired brain angiogenesis and neuronal apoptosis induced by conditional homozygous inactivation of vascular endothelial growth factor. Thromb Haemost 91: 595-605, 2004

Augustin HG, Breier G: Angiogenesis: molecular mechanisms and functional interactions. 2nd Kloster Seeon Meeting of the German Priority Research Grant "Angiogenesis" (SPP1069). Thromb Haemost 89: 190-97, 2003

Elvert G, Kappel A, Heidenreich R, Englmeier U, Lanz S, Acker T, Rauter M, Plate KH, Siewecke M, Breier G, Flamme I: Cooperative interaction of hypoxia-inducible factor-2a and Ets-1 in the transcriptional activation of Flk-1. J Biol Chem 278: 7520-30, 2003

Hirai H, Ogawa M, Suzuki N, Yamamoto M, Breier G, Mazda O, Imanishi J, Nishikawa SI (). Hemogenic and non-hemogenic endothelium can be distinguished by the activity of fetal liver kinase (Flk)-1 promoter/enhancer during mouse embryogenesis. Blood 101: 886-93, 2003

Issbrücker K, Marti HH, Hippenstiel S, Springmann G, Vosswinkel R, Gaumann A, Breier G, Drexler HCA, Suttorp N, Clauss M: p38 MAPK - a molecular switch between angiogenesis and vascular permeability. FASEB J 17: 262-264, 2003

Voswinckel R, Ziegelhoeffer T, Heil M, Kostin S, Breier G, Mehling T, Schaper W, Seeger W: Bone marrow derived cells do not contribute to compensatory lung growth. Circ Res 93: 372-9, 2003

 

 
 
 
 
 
 

 

 
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Impressum | Last update: 04/21/2009