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Xmrk‐induced melanoma progression is affected by Sdf1 signals through Cxcr7
Author(s) -
Liedtke Daniel,
Erhard Isabell,
Abe Keiko,
FurutaniSeiki Makoto,
Kondoh Hisato,
Schartl Manfred
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12188
Subject(s) - melanoma , biology , cancer research , in vivo , chemokine , genetically modified mouse , microphthalmia associated transcription factor , transgene , tumor progression , metastasis , oncogene , carcinogenesis , chemokine receptor , receptor , cancer , gene , genetics , transcription factor , cell cycle
Summary Chemokine signals mediated by S df1/ C xcl12 through the chemokine receptor C xcr4 are thought to play an instructive role in tumor migration and organ‐specific metastasis. We have used a small aquarium fish model to contribute to a better understanding of how the course of melanoma development is influenced by S df1 signals in vivo. We studied oncogene‐induced skin tumor appearance and progression in the transgenic medaka ( O ryzias latipes ) melanoma model. Similar to humans, invasive medaka melanomas show increased levels of sdf1 , cxcr4, and cxcr7 gene expression. Stable transgenic fish lines overexpressing sdf1 exclusively in pigment cells showed a reduction in melanoma appearance and progression. Remarkably, diminished levels of functional C xcr7, but not of C xcr4b, resulted in strongly reduced melanoma invasiveness and a repression of melanoma. Our results thereby indicate that S df1 signals via C xcr7 are able to constrain melanoma growth in vivo and that these signals influence tumor outcome.