Research Cluster #5 - CCC · PDF Cluster: Microenvironment, ... Nagy-Bojarszky K, Huttary N,...

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www.ccc.ac.at Cluster: Microenvironment, Vasculature and Metastasis

Research Cluster #5

Microenvironment, Vasculature & Metastasis

CoordinatorsMedhat Shehata / Dontscho Kerjaschki


A complex topic which offers many therapeutic targets

Adhesion

MoleculesIntegrins signaling

Matrix

component:Collagen, Fibronectin, Hyaluronan, Other matrix proteins

Soluble component:Cytokines, Chemokines, Growth factors

Cellular

component:B, T, NK cells Macrophages, DC, ECStromal cells, adipocytes

Cell motilty, migrarion &Drug resistance

Oncogenesis & Epithelial/mesenchymal transition

Angiogenesis&Lymph-angiogenesis

Tumor escape, Shedding, circulation &dissemination

Microenvironment, Vasculature & Metastasis

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Leukemia and solid tumor models & interconnection

LSC

EC EC

LCLSC

SC

Leukemia model

SC/TAF

TSC

TC

TSC

Solid tumor model

Tumor initiation, expansion, recirculation,origin, stem cells

Metastasis, dissemination,angiogenesis, lymphangiogenesis

CTC/DTC,Marrow micrometastasis


Participants, Departments & Institutes

1. Institut für Krebsforschung2. Universitätsklinik für Innere Med I: 3. Universitätsklinik für Innere Med II 4. Universitätsklinik für Innere Med III5. Klinisches Institut für Pathologie6. Universitätsklinik für Dermatologie7. Universitätsklinik für Blutgruppenserologie &

Transfusionmedizin8. Klinische Inst. Für Medizinische &

Chemische Labordiagnostik9. Universitätsklinik für Strahlentherapie10. Universitätsklinik für Chirurgie11. Universitätsklinik für Frauenheilkunde12. Institut für Pharmakologie13. CeMM - Centrum für molekulare Medizin14. St. Anna Kinderspital15. The Max F. Perutz Laboratories (MFPL)16. Institute of pharmacology and toxicology:17. University of Veterinary Medicine Vienna, VMW

- Registered participants: 65

- Clinicians &Basic Researchers

- 17 institutes

- Regular meetings: 2 times a year

- Working groups meetings: frequent

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Projects submitted by

members of the cluster

1- P. Petzelbauer: Wiener Wissenschafts-, Forschungs- und Technologiefonds 2011-2014 (LS11-008) 4-P.

2. Petzelbauer: FWF 2011-2014 (P24022-B21)3. Kerjaschki: TranSVIR - Translational Science for Vascular Inflammation and Remodelling (EU,

Project ID 238756; MUW: 1009k, 2009-2013)4. Kerjaschki: E-Rare – Epidermal growth factor system in rare glomerular disease (EU/FWF,

Project ID. I923-B13; MUW 157k, 2012-2014)5. W. Mikulits: EU-Project “IT-LIVER” FP7-PEOPLE-2012-ITN6. Shehata/Gerner: Secretome and proteom analysis of CLL microenvironment. IK-Forschung7. Shehata/ Holtzmann: Mesenchymal stem cells and telomerase. IK-Forschung8. M. Schreiber: Hallmarks of epithelial-mesenchymal transition in a panel of clinical human

breast cancer samples; Martin Schreiber; ÖNB; decision pending9. M. Schreiber: The role of a common polymorphism in the cyclooxygenase-2 promotor in breast

cancer; Katharina Tomek; DOCfforte of the Austrian academy of science; not funded10. Shehata/ Kerjaschki: CTC/DTC: CCC grant proposal: not funded11. Ch. Brostjan/E Hofer: NK cells: CCC grant proposal: not funded

More than 10 projects have been submitted, funded or bending


International & national academic cooperation

1. Petzelbauer/Erwin Wagner, Madrid, 2. Petzelbauer/Sandra Citi, Geneva, 3. Petzelbauer/Marcus Schultz, Amsterdam4. Petzelbauer/Kai Zacharowski, Frankfurt5. Kerjaschki / Prof V Sexl (VetMed); Kerjaschki / Prof M Swartz (ETH Lausanne)6. W. Mikulits: FWF-SFB “Jak-Stat”, "RESOLVE Chronic Inflammation and Achieve

Healthy Aging by Understanding Non-regenerative Repair. - Proj.Nr.: HEALTH-F4-2008-202047"

7. Shehata/J. Burger MD Anderson USA: CLL microenvironment8. Shehata/J. Burger MD Anderson USA: ALL/CXCR4 M. Schreiber: Membership and

cooperations within cluster 6 and 7. 9. M. Shehata/J. Vasicek: Slovak republic: hematopoietic stem cells 10. C. Brostjan/ collaboration with Cluster #4: Prof. Mac Felda and Markus Mandl11. M. Schreiber: Cooperations with other scientists at MUW, IMP and IMBA12. Proteome and secretome analysis M. Shehata/C. Gerner13. Mesenchymal Stem cells-Telomerase: M. Shehata/K. Holzmann 14. Shehata, Kerjaschki, DTC/CTC : 7 clusters, CCC grant application

At least 14 international coperation projects and exchange program between the research clusters have been initiated

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Cluster Database for exchangeof knowledge and materials (planned)

Activities


Selected Projects / Publications>32 papers: 198,4 IF>10 papers, CCC cited: 78,3 IF

1. Identification of a rational and highly effective therapy to treat NPM-ALKdriven lymphomas Daniela Laimer Daniela Laimer, Helmut Dolznig, Karoline Kollmann, Paul W. Vesely, Michaela Schlederer, Olaf Merkel, Ana-Iris Schiefer,Melanie R. Hassler, Susi Heider, Lena Amenitsch, Christiane Thallinger, Philipp B. Staber, Ingrid Simonitsch-Klupp,Matthias Artaker, Stefano Pileri, Pier Paolo Piccaluga, Peter Valent, Katia Messana, Indira Landra, Thomas Weichhart,Sylvia Knapp, Medhat Shehata, Maria, Veronika Sexl, Gerald Höfler, Roberto Piva, Enzo Medico, Gerda Egger, Josef M. Penninger, Ulrich Jaeger,Richard Morigg, Giorgio Inghirami and Lukas Kenner (Re-submitted to Nature).

2. Lipoxygenase mediates invasion of intrametastatic lymphatic vesselsand propagates lymph node metastasis of human mammary carcinomaxenografts in mouse. Zsuzsanna Bago-Horvath, Kerjaschki D, Bago-Horvath Z, Rudas M, Sexl V, Schneckenleithner C, Wolbank S, Bartel G, Krieger S, Kalt R, HantuschB, Keller T, Nagy-Bojarszky K, Huttary N, Raab I, Lackner K, Krautgasser K, Schachner H, Kaserer K, Rezar S, Madlener S, Vonach C, Davidovits A, Nosaka H, Hämmerle M, Viola K, Dolznig H, Schreiber M, Nader A, Mikulits W,Gnant M, Hirakawa S, Detmar M, Alitalo K, Nijman S, Offner F, Maier TJ, Steinhilber D, Krupitza G. (2011). The Journalof Clinical Investigation 121, 2000- 2012. IF: 14.152 (CCC cited)

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Identification of a rational and highly effective therapyto treat NPM-ALK driven

lymphomas Mag. Daniela Laimer

Clinical Institute of Pathology, Medical University of Vienna


NPM-ALKJun mice survive 75% longer than control mice

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PDGFRβ is a novel direct AP-1 target, blockage significantly lowers tumor size in vivo


Blockage of PDGFRβ in a terminal human NPM-ALK positive ALCL patient lead to full remission

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Model

FOLIEN TEXT


Acknowledgements

Gerald Höfler,

Paul Vesely,

Phillipp Staber,

Institute of Pathology,

Medical University of Graz

Lukas KennerGerda Egger,Michaela Schlederer Richard MorigglMelanie HasslerLena Amenitsch

Inst. of clinical Pathology, MUW/Ludwig Boltzmann Institute of Cancer Research Vienna

Josef PenningerArabella MeixnerIMBA Vienna

Christiane ThallingerMedhat ShehataUllrich Jäger1. Med. Univ. Clinic MUW

Erwin F. Wagner, CNIO Madrid

Giorgio Inghirami, Inst. Pathol. Univ. Turino

Karoline KollmannVeronika Sexl

University of Vet. Medicine, Vienna

Helmut DolznigInst. of Medical Genetics, MUW

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Mechanisms of lymph node metastasis in breast cancer

Kerjaschki et al, J Clin Invest. 2011;121(5):2000‐12.


GAP formation in LV by tumor cell clusters

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N0 N1 N2/3

Ductal Carcinoma (n=76) ‐‐‐‐ 0% 100%

Lobular Carcinoma (n=37) ‐‐‐‐ 6% 58%

Intrametastatic lymphatic tumor embolization is predictive of post‐sentinel lymph node involvement

Kerjaschki et al, J Clin Invest.2011 May 2;121(5):2000‐12. doi: 10.1172/JCI44751.


MCF-7 spheroid induce gap formationin LEC monolayers


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15-LO knock down reducesgap formation



Xenograft experiments

Xenografts of MCF-7 / VEGF-C cellsplus / minus 15 LOX knockdown


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Acknowledgements

Dontscho KerjaschkiMargaretha Rudas

Georg KrupitzaBrigitte Hantusch

Michael GnantPeter DubskyRuth Exner

Kari Alitalo

Thomas Helbich

Veronika SexlChristine Schneckenleithener

Susanne WolbankMartin Schreiber

Romana KaltSigurd KriegerNicole Huttary

Ingrid RaabHelga Schachner

Karin Lackner

Thorsten MeierDieter Steinhilber

Research Cluster #5 - CCC · PDF Cluster: Microenvironment, ... Nagy-Bojarszky K, Huttary N,...

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