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
 


Dr. Heike Beck and
Dr. Heike Beck
Institute of Physiology
Walter-Brendel-Center for Experimental Medicine
Ludwig-Maximilians University Munich
Marchioninistr. 15
D-81377 Munich, Germany
 
Tel: ++49 (0) 89-218076537
Fax: ++49 (0) 89-218076532

Lab Homepage

heike.beck(at)med.uni-muenchen.de


Dr. Marcus Conrad
Dr. Marcus Conrad
Helmholtz Zentrum München
Institute of Clinical Molecular Biology and
Tumor Genetics
Marchioninistr. 25
D-81377 Munich, Germany

Tel: ++49 (0) 89-7099525
Fax: ++49 (0) 89-7099500

Lab Homepage

marcus.conrad@helmholtz-muenchen.de

 
The contribution of redox regulation in tumor angiogenesis and tumor growth: glutathione peroxidase 4 GPx4) as a key regulator of 12/15-lipoxygenase activity
Tumor growth requires sustained supply of nutrition and oxygen. When this is no longer guaranteed due to limited diffusion within rapidly growing tumors, tumor cells induce neo-vascularization ("angiogenic switch"). Pro-carcinogenic and pro-angiogenic key molecules include hypoxia-inducible factor, vascular endothelial growth factors, angiopoietins and their cognate receptor as well as enzymes of the arachidonate metabolism, such as cyclooxygenases and lipoxygenases. Phospholipid hydroperoxide glutathione peroxidase (PHGPx), major regulator of cellular peroxide tone, counteracts cyclooxygenase and lipoxygenase activities. By conditional inactivation of PHGPx in primary mouse embryonic fibroblasts and embryonic stem cells we shall unravel the basic biochemical mechanisms of PHGPx in arachidonic and linoleic acid metabolism. In addition we plan to analyze multiple steps in the angiogenic cascade, including endothelial cell proliferation, migration and differentiation in PHGPx-deficient embryonic endothelial precursor cells. Two complementary transplantation approaches in mice will be performed to address the effect of PHGPx-deficiency on tumor growth and tumor angiogenesis both in the tumor compartment and in the host-derived vascular compartment. These studies will provide us with novel insights into redox-regulated tumor angiogenesis.
 
- Relevant recent publications -

Beck H, Semisch M, Culmsee C, Plesnila N, Hatzopoulos AK. Egr-1 regulates expression of the glial scar component Phosphacan in astrocytes after experimental stroke. Am J Pathol, in press

Soerensen J, Jakupoglu C, Beck H, Förster H, Schmidt J, Schmahl W, Schweizer U, Conrad M, Brielmeier M. The role of thioredoxin reductases in brain development. PLoS ONE. 2008 Mar 19;3(3):e1813.

Conrad M, Schneider M, Seiler A, Bornkamm GW. Physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals. Biol Chem. 2007 Oct;388(10):1019-25. Review.

Banjac A, Perisic T, Sato H, Seiler A, Bannai S, Weiss N, Kölle P, Tschoep K, Issels RD, Daniel PT, Conrad M, Bornkamm GW. The cystine/cysteine cycle: a redox cycle regulating susceptibility versus resistance to cell death. Oncogene. 2008 Mar 6;27(11):1618-28. Epub 2007 Sep 10.

 
 
 
 
 
 

 

 
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Impressum | Last update: 06/26/2008