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 Friedl

 

Rudolf-Virchow-Center for Experimental Biomedicine
University of Würzburg
Versbacher Str. 9
D-97078 Würzburg
Phone: ++49 (0) 9 31-2 01 26 737
Fax: ++49 (0) 9 31-2 01 26 700

Lab Homepage

peter.friedl(at)virchow.uni-wuerzburg.de

 

 
Vessel-guided collective cancer invasion in vivo: molecular mechanisms and fate
Cancer invasion and metastasis are the result of promigratory activity in tumor cells which is in part induced and directed by structural and molecular signals provided by the tumor microenvironment. The tumor vasculature represents both, a tructural and molecular scaffold for tumor cell invasion. Structurally, vessels provide aligned fibrillar and basement membrane ECM structures together with elongated endothelial cell bodies for direct domains engaging integrins, released MMPs and other proteases for receptor processing, and cell surface molecules supporting heterophilic cellular interactions, including ephrin-B2/EphB4, N-/VE-cadherin, or NCAM. We investigate how tumor vessels and neovessels contribute to tumor cell invasion by using dynamics imaging in 3D ECM based confrontation assays as well as intravital multiphoton microscopy of GFP/RFP expressing tumor cells in the nestin/GFP nude mouse. Using time-resolved topographic reconstruction and interference with soluble antagonists or RNAi, target functions will be ECM remodeling for guided migration and the provision of basement membrane and other aligned ECM structure. A key focus aims at direct heterologous tumor cell-EC interactions via Ephrin/EphB pathways mediating dynamic cell-cell contacts. Concepts will be established using ECM in vitro confrontation assays and then validated by intravital multiphoton microscopy. These studies will provide new concepts on molecular switches of tumor invasion beyond integrin-mediated cell-matrix interactions.
 
- Relevant recent publications -

Cam H, Griesmann H, Beitzinger M, Hofmann L, Beinoraviciute-Kellner R, Sauer M, Huttinger-Kirchhof N, Oswald C, Friedl P, Gattenlohner S, Burek C, Rosenwald A, Stiewe T: p53 family members in myogenic differentiation and rhabdomyosarcoma development. Cancer Cell 10: 281-93, 2006

Wolf K, Friedl P: Molecular mechanisms of cancer cell invasion and plasticity. Br J Dermatol 154: 11-5, 2006

Hartmann A, Boukamp P, Friedl P: Confocal reflection imaging of 3D fibrin polymers. Blood Cells Mol Dis 36: 191-3, 2006

Friedl P: Cell fusion: new mechanisms of plasticity in cancer? Lancet Oncol 6: 916-8, 2005

Friedl P, den Boer AT, Gunzer M: Tuning immune responses: diversity and adaptation of the immunological synapse. Nat Rev Immunol 5: 532-45, 2005

Wolf K, Friedl P: Functional imaging of pericellular proteolysis in cancer cell invasion. Biochimie 87: 315-20, 2005

Mayer C, Maaser K, Daryab N, Zanker KS, Brocker EB, Friedl P: Release of cell fragments by invading melanoma cells. Eur J Cell Biol 83: 709-15, 2004

Friedl P, Storim J: Diversity in immune-cell interactions: states and functions of the immunological synapse. Trends Cell Biol 14: 557-67, 2004

Friedl P, Hegerfeldt Y, Tusch M: Collective cell migration in morphogenesis and cancer. Int J Dev Biol 48: 441-9, 2004

Uhlenbrock K, Eberth A, Herbrand U, Daryab N, Stege P, Meier F, Friedl P, Collard JG, Ahmadian MR: The RacGEF Tiam1 inhibits migration and invasion of metastatic melanoma via a novel adhesive mechanism. J Cell Sci 117: 4863-71, 2004

Friedl P: Dynamic imaging of cellular interactions with extracellular matrix. Histochem Cell Biol 122: 183-90, 2004

Gunzer M, Weishaupt C, Hillmer A, Basoglu Y, Friedl P, Dittmar KE, Kolanus W, Varga G, Grabbe S: A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivo. Blood 104: 2801-9, 2004

Friedl P: Dynamic imaging of the immune system. Curr Opin Immunol 16: 389-93, 2004

Friedl P: Prespecification and plasticity: shifting mechanisms of cell migration. Curr Opin Cell Biol 16: 14-23, 2004

Friedl P, Brocker EB: Reconstructing leukocyte migration in 3D extracellular matrix by time-lapse videomicroscopy and computer-assisted tracking. Methods Mol Biol 239: 77-90, 2004

Wolf K, Muller R, Borgmann S, Brocker EB, Friedl P: Amoeboid shape change and contact guidance: T-lymphocyte crawling through fibrillar collagen is independent of matrix remodeling by MMPs and other proteases. Blood 102: 3262-9, 2003

Friedl P, Wolf K: Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3: 362-74, 2003

Wolf K, Mazo I, Leung H, Engelke K, von Andrian UH, Deryugina EI, Strongin AY, Brocker EB, Friedl P: Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J Cell Biol 160: 267-77, 2003

Friedl P, Brocker EB: TCR triggering on the move: diversity of T-cell interactions with antigen-presenting cells. Immunol Rev 186: 83-9, 2002

Hegerfeldt Y, Tusch M, Brocker EB, Friedl P: Collective cell movement in primary melanoma explants: plasticity of cell-cell interaction, beta1-integrin function, and migration strategies. Cancer Res 62: 2125-30, 2002

 

 
 
 
 
 
 

 

 
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Impressum | Last update: 06/26/2008