Xmrk‐induced melanoma progression is affected by Sdf1 signals through Cxcr7 |
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| Authors: | Daniel Liedtke Isabell Erhard Keiko Abe Makoto Furutani‐Seiki Hisato Kondoh Manfred Schartl |
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| Institution: | 1. Department of Physiological Chemistry, University of Würzburg, Biozentrum, , Würzburg, Germany;2. Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, , Tokyo, Japan;3. Department of Biology and Biochemistry, Centre for Regenerative Medicine, University of Bath, , Bath, UK;4. Graduate School of Frontier Biosciences, Osaka University, , Osaka, Japan;5. Comprehensive Cancer Center, University Clinic Würzburg, , Würzburg, Germany |
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| Abstract: | Chemokine signals mediated by Sdf1/Cxcl12 through the chemokine receptor Cxcr4 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 Sdf1 signals in vivo. We studied oncogene‐induced skin tumor appearance and progression in the transgenic medaka (Oryzias 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 Cxcr7, but not of Cxcr4b, resulted in strongly reduced melanoma invasiveness and a repression of melanoma. Our results thereby indicate that Sdf1 signals via Cxcr7 are able to constrain melanoma growth in vivo and that these signals influence tumor outcome. |
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| Keywords: | Sdf1 Cxcl12 Cxcr7 Cxcr4 Xmrk medaka melanoma |
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