Lymphangiogenomics

Metastatic spreading of tumor cells to local lymph nodes is a frequent early event in malignant tumor progression. An increasing body of evidence now indicates that lymphangiogenic stimuli are involved in the lymphatic dissemination of tumor cells. The major goal of this part of the Integrated Project is to understand the molecular regulation of lymphangiogenesis in the context of tumor development and the functional contribution of lymphangiogenesis (as compared to blood vessel angiogenesis) to tumor progression and to the metastatic dissemination of tumor cells.

Responsible for this project:

Dr. Gerhard Christofori

Dept. of Clinical-Biological Sciences

Institute of Biochemistry and Genetics

University of Basel

Vesalgasse 1

4051 Basel, Switzerland

Phone: +41 61 267 3562

Fax: +41 61 267 3566

E-mail: gerhard.christofori(at)unibas.ch

Selected recent publications:

1. Schomber T, Zumsteg A, Strittmatter K, Crnic I, Antoniadis H, Littlewood-Evans A, Wood J, Christofori G.Differential effects of the vascular endothelial growth factor receptor inhibitor PTK787/ZK222584 on tumor angiogenesis and tumor lymphangiogenesis. Mol Cancer Ther. 8(1):55-63, 2009.
    

2. Schomber T, Kopfstein L, Djonov V, Albrecht I, Baeriswyl V, Strittmatter K, Christofori G. Placental growth factor-1 attenuates vascular endothelial growth factor-A-dependent tumor angiogenesis during beta cell carcinogenesis. Cancer Res. 15;67(22):10840-8, 2007.
    
3. Kopfstein L, Veikkola T, Djonov VG, Baeriswyl V, Schomber T, Strittmatter K, Stacker SA, Achen MG, Alitalo K, Christofori G.

   Distinct roles of vascular endothelial growth factor-D in lymphangiogenesis and metastasis. Am J Pathol. 170(4):1348-61, 2007.
    

4. Francavilla, C., Loeffler, S., Piccini, D., Kren, A., Christofori, G., and Cavallaro, U. Neural cell adhesion molecule regulates the cellular response to fibroblast growth factor. J. Cell Sci. 120, 4388-4394, 2007.
    

5. Schomber, T., Kopfstein, L., Djonov, V., Albrecht, I., Baeryiswyl, V., Strittmatter, K., and Christofori G. Placental growth factor-1 attenuates vascular endothelial growth factor-A-dependent tumor angiogenesis during = cell carcinogenesis. Cancer Res. 67, 10840-10848, 2007.
    

6. Kren, A., Baeriswyl, V., Lehembre, F., Wunderlin, C., Strittmatter, K., Antoniadis, H., Fässler, R., Cavallaro, U., and Christofori, G. Increased tumor cell dissemination and cellular senescence in the absence of =1-integrin function. EMBO J 26, 2832-2842, 2007.
    

7. Wicki, A., Wild, D., Storch, D., Seemayer, C., Béhé, M., Gotthardt, M., Kneifel, S., Mihatsch, M., Reubi, J.C., Mäcke, H.R., and Christofori, G. A new therapeutic approach to insulinoma: [(Lys40(Ahx-[111In-DTPA])]-Exendin-4 is a highly efficient radiotherapeutic for glucagon-like peptide-1 (GLP-1) receptor-targeted therapy. Clinical Cancer Res. 13, 3696-3705, 2007.
    

8. Terada N, Ohno N, Yamakawa H, Baba T, Fujii Y, Christofori G, Ohara O, Ohno S. Protein 4.1B in mouse islets of Langerhans and beta-cell tumorigenesis. Histochem Cell Biol 120:277-283, 2003.
    

9. Perl AK, Hokuto I, Impagnatiello MA, Christofori G, Whitsett JA. Temporal effects of Sprouty on lung morphogenesis. Dev Biol 258:154-168, 2003.
    

10. Gannon G, Mandriota SJ, Cui L, Baetens D, Pepper MS, Christofori G. Overexpression of vascular endothelial growth factor-A165 enhances tumor angiogenesis but not metastasis during beta-cell carcinogenesis. Cancer Res 62:603-608, 2002.
     

11. Cavallaro U, Niedermeyer J, Fuxa M, Christofori G. N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling. Nat Cell Biol 3:650-657, 2001.
     

12. Impagnatiello MA, Weitzer S, Gannon G, Compagni A, Cotten M, Christofori G. Mammalian sprouty-1 and -2 are membrane-anchored phosphoprotein inhibitors of growth factor signaling in endothelial cells. J Cell Biol 152:1087-1098, 2001.
     

13. Mandriota SJ, Jussila L, Jeltsch M, Compagni A, Baetens D, Prevo R, Banerji S, Huarte J, Montesano R, Jackson DG, Orci L, Alitalo K, Christofori G, Pepper MS. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J 20:672-682, 2001.
     

14. Compagni A, Wilgenbus P, Impagnatiello MA, Cotten M, Christofori G. Fibroblast growth factors are required for efficient tumor angiogenesis. Cancer Res 60:7163-7169, 2000.

Reviews:

8.  Cavallaro U, Christofori G. Multitasking in tumor progression: signaling functions of cell adhesion molecules. Ann N Y Acad Sci 1014:58-66, 2004.
    

9. Cavallaro U, Christofori G. Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer 4:118-132, 2004.
    

10. Cabrita MA, Christofori G. Sprouty proteins: antagonists of endothelial cell signaling and more. Thromb Haemost 90:586-590, 2003.
     

11. Christofori G. Changing neighbours, changing behaviour: cell adhesion molecule-mediated signalling during tumour progression. EMBO J 22:2318-2323, 2003.
     

12. Christofori G. Split personalities: the agonistic antagonist Sprouty. Nat Cell Biol 5:377-379, 2003.
     

13. Herzig M, Christofori G. Recent advances in cancer research: mouse models of tumorigenesis. Biochim Biophys Acta 1602:97-113, 2002.
     

14. Cavallaro U, Schaffhauser B, Christofori G. Cadherins and the tumour progression: is it all in a switch? Cancer Lett 176:123-128, 2002.
     

15. Cavallaro U, Christofori G. Cell adhesion in tumor invasion and metastasis: loss of the glue is not enough. Biochim Biophys Acta 1552:39-45, 2001.
     

16. Cavallaro U, Christofori G. Molecular mechanisms of tumor angiogenesis and tumor progression. J Neurooncol 50:63-70, 2000.
     

17. Compagni A, Christofori G. Recent advances in research on multistage tumorigenesis. Br J Cancer 83:1-5, 2000.