Wnt1 is anti-lymphangiogenic in a melanoma mouse model

Heide Niederleithner, Magdalena Heinz, Stefanie Tauber, Martin Bilban, Hubert Pehamberger, Stefan Eugen Sonderegger, Martin Knofler, Andreas Bracher, Walter Berger, Robert Loewe, Peter Petzelbauer

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16 Citations (Scopus)


Wnt signals contribute to melanoma progression by boosting their proliferation and survival. Initially, we expected that activated Wnt signaling also improves their proficiency to recruit blood and lymph vessels. To assess this, we added cell culture supernatants (SNs) of Wnt1 and Wnt1 melanoma to endothelial spheroids. Whereas SNs of Wnt1 - melanoma cells induced lymphatic sprouts, those of Wnt1 + cells were unable to do so and this was restored by vascular endothelial growth factor C (VEGF-C). Subsequent testing of several human melanoma lines revealed that Wnt1 suppressed their VEGF-C expression. This Wnt1 effect did not depend on glycogen synthase kinase-3I? (GSK3I?), I?-catenin, or activator protein-1, but was blocked by cyclosporine A (CsA). To analyze Wnt1 effects in melanoma in vivo, we selected Wnt1 melanoma cell lines, overexpressed Wnt1, and injected them subepidermally into severe combined immunodeficient (SCID) mice. We found reduced VEGF-C expression, reduced lymphangiogenesis, and delayed metastasis to sentinel nodes in Wnt1 as compared with Wnt1 - melanoma (P
Original languageEnglish
Pages (from-to)2235 - 2244
Number of pages10
JournalJournal of Investigative Dermatology
Issue number9
Publication statusPublished - 2012

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