Wnt1 is anti-lymphangiogenic in a melanoma mouse model.

The Journal of Investigative Dermatology
Heide NiederleithnerPeter Petzelbauer

Abstract

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-3β (GSK3β), β-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<0.05). Concomitant overexpression of VEGF-C or feeding of animals with CsA restored lymphangiogenesis and metastasis in Wnt1(+) melanoma. In co...Continue Reading

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Citations

Jan 25, 2013·International Journal of Molecular Sciences·Jui-Chieh ChenJen-Liang Su
Aug 2, 2014·The Journal of Investigative Dermatology·Magdalena HeinzPeter Petzelbauer
Feb 2, 2016·The Journal of Investigative Dermatology·Emmi PuujalkaPeter Petzelbauer
Jan 16, 2015·Biology of Reproduction·Laila F Jerman, Alison J Hey-Cunningham
Feb 25, 2014·Nature Reviews. Cancer·Steven A StackerMarc G Achen
Feb 19, 2019·Médecine sciences : M/S·Papa Diogop Ndiaye, Gilles Pagès
Sep 7, 2021·Medicinal Research Reviews·Sara RezzolaRoberto Ronca

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