Fibroblast growth factors and their receptors in melanoma and mesothelioma

The 22 human fibroblast growth factors and the four high affinity fibroblast growth factor receptors constitute a powerful signaling system involved in regulation of cell growth, cell death, differentiation and migration in embryogenesis and throughout adult life. Tumors frequently hijack certain FGFs and/or FGFRs to sustain their own growth, blood supply, invasion and colonization of distant organs. Our group analyzes their expression and function in melanoma and malignant pleural mesothelioma. In these two hard-to-treat malignancies our research demonstrated important functions especially of FGFR1 and of FGFs 2, 5 and 18 in tumor progression and drug resistance. Consequently inhibition of FGFR signals shows synergistic activity when combined with BRAF inhibition (melanoma) or cisplatin and radiation (mesothelioma).

Figure: Adenoviral transduction of human melanoma cells with a green fluorescent protein (GFP)-tagged dominant negative FGF-receptor 1 (dnFGFR1-GFP) inhibits growth and increases apoptosis in comparison to cells transduced with a control adenovirus expressing only GFP (for Reference see Metzner et al. 2011).

Students: Karin Schelch, Christine Wagner

Collaborations: The ICR FGF Focus Group (Walter Berger, Brigitte Marian, Bettina Grasl-Kraupp, Klaus Holzmann), the Thoracic Oncology Lab (Balazs Hegedüs, Balazs Döme, Mir Alireza Hoda, Division of Thoracic Surgery, Medical University of Vienna, The Isaac Witz Lab, Tel Aviv University, the Glen Reid Lab, Asbestos Disease Research Institute, Sydney).

Financial support: Anniversary Fund of the Austrian National Bank, Herzfelder Foundation

Research Focus: Development of Experimental Cancer Therapies