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. Peter Vajkoczy

 

Prof. Dr. Peter Vajkoczy
Neurochirurgische Klinik und Poliklinik
(Dept of Neurosurgery)
Charité - Universitätsmedizin Berlin
Augustenburger Platz 1
D-13344 Berlin, Germany
 
Tel: ++49 (0) 30 450 560 002
Fax: ++49 (0) 30 450 560 900

Lab Homepage

 

 

peter.vajkoczy(at)charite.de

 

 
 
Interaction between the microglia and blood vessels in malignant brain tumors - significance for brain tumor angiogenesis, vascular modulation, and brain tumor growth
The pathology of malignant brain tumors is characterized by multiple cellular interactions at the interface between blood vessels and tumor cells. For example, the cellular components of the vessel wall continuously interact with each other and with tumor cells during angiogenesis. Furthermore, the perivascular space is the preferred route of local tumor spread while, at the same time, tumor cells are restricted from invading the cerebral cortex or vascular lumen. Since the guidance molecules ephrinB2 and EphB4 are expressed by brain tumor cells as well as by cells of the vessel wall, and are activated upon cell/cell-interaction to affect cell adhesion and migration, we hypothesize that they play a central role in these cellular interactions at the blood vessel-tumor cell interface. To test this, we will first extend our previous studies on the role of vascular ephrinB2/EphB4 signaling for vascular morphogenesis in tumors. Vascular ephrinB2 reverse signaling will be manipulated by an in vivo retroviral approach and by using a conditional, endothelial cell-specific ephrinB2-deficient mouse. We will also analyze whether vascular ephrinB2/EphB4 signaling is involved in intussusceptive blood vessel growth and may, thereby, represent a novel mediator of this hitherto incompletely understood angiogenic process. Second, we will study the role of tumor cellular ephrinB2/Eph4 signaling for brain tumor cell migration and invasion and we will test the hypothesis that ephrinB2/EphB4 may act as a ´compartmentalization factor´ for brain tumor cells, directing them into their preferred perivascular route of local dissemination. To test this we will transfect tumor cells with EphB4 variants or knock-down EphB4 expression by siRNA and study the consequences on tumor cell migration/invasion. Third, we will address the effects of tumor cellular ephrinB2/Eph4 signaling on the tumor vascular phenotype. Therefore, we will xenograft the EphB4 manipulated tumor cells and study the resultant morphology and architecture of the tumor vascular system as well as the composition of the blood vessel wall. By applying our versatile combination of in vitro assays and in vivo imaging techniques, we will provide a unique insight into the role of ephrinB2/EphB4 signaling at the blood vessel - tumor cell interface of malignant brain tumors.
 
- Relevant recent publications -

Erber R, Eichelsbacher U, Powajbo V, Korn T, Djonov V, Lin J, Hammes HP, Grobholz R, Ullrich A, Vajkoczy P EphB4 controls blood vascular morphogenesis during postnatal angiogenesis. EMBO J 2006 Jan 19, in press

Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, Gale NW, Witzenrath M, Rosseau S, Suttorp N, Sobke A, Herrmann M, Preissner KT, Vajkoczy P, Augustin HG: Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med 12: 235 - 239, 2006

Hoffmann J, Feng Y, vom Hagen F, Hillenbrand A, Lin J, Erber R, Vajkoczy P, Gourzoulidou E, Waldmann H, Wolburg H, Shani M, Jaeger V, Weich HA, Preissner K, Hoffmann S, Deutsch U, Hammes HP. Endothelial survival factors, but not pericyte coverage of retinal capillaries determine responsiveness to vasoregression in the retina. FASEB J 19: 2035-6, 2005

Laschke MW, Elitzsch A, Vollmar B, Vajkoczy P, Menger MD: Combined inhibition of vascular endothelial growth factor (VEGF), fibroblast growth factor and platelet-derived growth factor, but not inhibition of VEGF alone, effectively suppresses angiogenesis and vessel maturation in endometriotic lesions. Hum Reprod 21: 262-8, 2006

Farhadi MR, Capelle HH, Erber R, Ullrich A, Vajkoczy P: Combined inhibition of VEGF- and PDGF-signalling: effects on orthotopic malignant glioma angiogenesis, microcirculation, and growth. J Neurosurg 102: 363-70, 2005

Urbich C, Heeschen C, Aicher A, Sasaki K, Bruhl T, Farhadi MR, Vajkoczy P, Hofmann WK, Peters C, Pennacchio LA, Abolmaali ND, Chavakis E, Reinheckel T, Zeiher AM, Dimmeler S: Cathepsin L is required for endothelial progenitor cell-induced neovascularization. Nat Med 11: 206-13, 2005

Tuettenberg J, Grobholz R, Korn T, Wenz F, Erber R, Vajkoczy P: Continuous low dose chemotherapy plus inhibition of cyclooxygenase-2 as an antiangiogenic therapy of glioblastoma multiforme. J Cancer Res Clin Oncol 131: 31-40, 2005

Erber R, Thurnher A, Katsen AD, Groth G, Kerger H, Hammes HP, Menger MD, Ullrich A, Vajkoczy P: Combined inhibition of VEGF- and PDGF-signalling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J 18: 338-40, 2004

Vajkoczy P, Blum S, Lamparter M, Mailhammer R, Erber R, Engelhardt B, Vestweber D, Hatzopoulos AK: Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis. J Exp Med 197: 1755-65, 2003

Schramm R, Yamauchi J, Vollmar B, Vajkoczy P, Menger MD: Blockade of in vivo VEGF-KDR/flk-1 signaling does not affect revascularization of freely transplanted pancreatic islets. Transplantation 75: 239-42, 2003

Kerger H, Groth G, Kalenka A, Vajkoczy P, Tsai AG, Intaglietta M: pO(2) measurements by phosphorescence quenching: characteristics and applications of an automated system. Microvasc Res 65: 32-8, 2003

 
 
 
 
 
 
 

 
 
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Impressum | Last update: 04/24/2009