Department of Dermatology
Skin and Endothelium Research Division
Waehringer Guertel 18-20, 1090 Vienna, Austria
Phone: +43 (0)1 40400 - 73716
Lymph node metastasis has been acknowledged to be the first hallmark of advanced stage malignancies. Metastasis usually means a worse clinical prognosis with mortality rates exceeding 50%; therefore, identification of leading signaling networks controlling lymphogenic metastasis remains a major challenge. My group is interested in the identification and functional assessment of tumor- and stromal-derived factors that influence metastatic behavior. Due to the lab´s position at the crossroads between basic research and clinical service, we follow a translational approach in our research projects.
We recently identified an important role of secreted EGF on primary melanoma lymphangiogenesis and lymph node metastasis (Bracher, et al. 2012). At the current stage we now aim to analyze EGF-mediated lymphangiogenic effects and to describe involved signaling networks. Identification of EGF-mediated tumor promoting effects via EGFR signaling in the tumor microenvironment could overcome the restriction of EGFR-targeted therapy to malignancies with EGFR-negative tumor cells.
The newly developed and in our laboratory established technique of DNA and RNA isolation out of formalin-fixed, paraffin embedded human tissue samples enables us to analyze angiogenic and lymphangiogenic factors in human tumor tissue. We currently determine subgroups of primary melanomas according to their angiogenic/lymphangiogenic potential to identify marker profiles for treatment decision and prognostic considerations.
The role of tumor- and stromal-derived soluble factors in the mediation of metastasis
Diverse basic molecular and cellular biology techniques (rt-PCR, Western Blot, IP), immunological and functional assays, flow cytometry, immunohistochemistry, image analysis, confocal microscopy, expression and purification of recombinant proteins, knockdown, silencing and overexpression of genes in vitro, animal models of tumor invasion and metastasis, transgenic animals.
A. Bracher, A. Soler-Cardona, S. Tauber, AM. Fink, A. Steiner, H. Pehamberger, H. Niederleithner, P. Petzelbauer, M. Gröger, R. Loewe. Epidermal growth factor facilitates melanoma lymph node metastasis by influencing tumor lymphangiogenesis. J Invest Dermatol. 2012 Sep 6, 272.
V. Leksa, R. Loewe, B. Binder, HB. Schiller, P. Eckerstorfer, F. Forster, A. Soler Cardona, G. Ondrovičová, E. Kutejová, E. Steinhuber, J. Breuss, P. Petzelbauer, BR. Binder, J. Drach, H. Stockinger. Soluble M6P/IGF2R released by TACE controls angiogenesis via blocking plasminogen activation. Circulation Research, 2011 Mar 18;108(6):676-85.
T. Valero, S. Steele, K. Neumüller, A. Bracher, H. Niederleithner, H. Pehamberger, P. Petzelbauer, R. Loewe. A combination of Dacarbazine and Dimethylfumarate efficiently reduces lymph node metastasis and tumor cell migration in a metastasizing mouse melanoma model. J Invest Dermatol, 2010 Apr;130(4):1087-94
R. Loewe, T. Valero, S. Kremling, B. Pratscher, R. Kunstfeld, H. Pehamberger, P. Petzelbauer. Dimethylfumarate impairs melanoma growth and metastasis. Cancer Res, 2006 Dec15;66(24).
R. Loewe, W. Holnthoner, M. Gröger, M. Pillinger, F. Gruber, D. Mechtcheriakova, E. Hofer, K. Wolff, P. Petzelbauer. Dimethylfumarate inhibits TNF-induced nuclear entry of NF-kappa B/p65 in human endothelial cells. J Immunol, 2002 May 1;168(9): 4781-7.