Wnt-signalling in melanoma-induced angiogenesis
Lymphoid enhancer factor (Lef) and T-cell factor (Tcf) proteins belong to a family of transcription factors which are typically induced by the canonical wnt signaling pathway. This pathway involves nuclear translocation of β-catenin, the formation of Lef/ Tcf/ β-catenin complexes and Lef/ Tcf-dependent transcription. Wnt signaling plays an important role in differentiation, organ development and cell growth. There is increasing evidence that wnt may also play a role in vessel formation in cancer.
It was the aim of this project to explore the role of wnt proteins in tumor blood and lymph vessel angiogenesis and to correlate this with melanoma growth and metastasis to sentinel nodes. We use a SCID model engrafted with human melanoma cells. In this model, primary melanoma is induced in the skin and metastasizes to the sentinel node in a way reminiscent of the situation in humans. By transgene expression in melanoma cells this system allows us to analyze the effects of modified gene expression on lymph-angiogenesis and metastasis. By using transgenic mice, we can analyze analyze the impact of stromal genes on melanoma progression.
This figure indicates a spheroid sprouting assay. Spheroids were generated by using HUVEC cells and methyl cellulose, and they were embedded into a collagen gel. HUVEC were treated with VEGF (50ng/ml) as a positive control and with control, wnt-1 and/ or DKK-1 supernatants from M24 cells. Pictures were taken 24h later.
Publications
- Fibroblast growth factor-2 induces Lef/Tcf-dependent transcription in human endothelial cells.
Holnthoner W, Pillinger M, Groger M, Wolff K, Ashton AW, Albanese C, Neumeister P, Pestell RG, Petzelbauer P. J Biol Chem. 2002 Nov 29;277(48):45847-53. Epub 2002 Sep 15.
