title: Xmrk-induced melanoma progression is affected by Sdf1 signals through Cxcr7.
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.
authors.affiliation: Department of Physiological Chemistry, University of Würzburg, Biozentrum, Würzburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Liedtke
authors.forename: Isabell
authors.initials: I
authors.lastname: Erhard
authors.forename: Keiko
authors.initials: K
authors.lastname: Abe
authors.forename: Makoto
authors.initials: M
authors.lastname: Furutani-Seiki
authors.forename: Hisato
authors.initials: H
authors.lastname: Kondoh
authors.forename: Manfred
authors.initials: M
authors.lastname: Schartl
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism*; D003433:Crosses, Genetic; D018450:Disease Progression; D005260:Female; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009990:Oryzias / Q000378:metabolism*; D010641:Phenotype; D010858:Pigmentation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D054387:Receptors, CXCR / Q000378:metabolism*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000201:enzymology / Q000473:pathology*
chemical_list: D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D020794:Receptor Protein-Tyrosine Kinases
keywords: Cxcl12; Cxcr4; Cxcr7; Sdf1; Xmrk; medaka; melanoma