TY - JOUR
T1 - Wnt1 is anti-lymphangiogenic in a melanoma mouse model
AU - Niederleithner, Heide
AU - Heinz, Magdalena
AU - Tauber, Stefanie
AU - Bilban, Martin
AU - Pehamberger, Hubert
AU - Sonderegger, Stefan Eugen
AU - Knofler, Martin
AU - Bracher, Andreas
AU - Berger, Walter
AU - Loewe, Robert
AU - Petzelbauer, Peter
PY - 2012
Y1 - 2012
N2 - 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
AB - 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
UR - http://www.nature.com/jid/journal/v132/n9/pdf/jid2012138a.pdf
U2 - 10.1038/jid.2012.138
DO - 10.1038/jid.2012.138
M3 - Article
SN - 0022-202X
VL - 132
SP - 2235
EP - 2244
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 9
ER -