Xmrk-induced melanoma progression is affected by Sdf1 signals through Cxcr7.

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.

snail gene expression in the medaka, Oryzias latipes.

Snail transcription factors have prominent roles during embryonic development of vertebrates. They are often involved in cell migration processes during neural crest development, epithelial-mesenchymal transition and cancer progression. Comparative expression studies of snai gene family members in different vertebrate species are expected to contribute to a better understanding of their roles during development and reflect their evolutionary history. To investigate and to compare the expression patterns of snai genes in a second main fish model we used the medaka fish (Oryzias latipes), a complementary teleost model to zebrafish. We identified three snai gene family members, snai1a, snai1b and snai2. Phylogenetic and synteny analysis show a close relatedness of all family members to other vertebrate snai genes. Surprisingly, no homologue of snai3 could be identified in medaka, although this gene is present in zebrafish and the puffer fishes. Here we demonstrate that while most expression domains of medaka snai genes are comparable to zebrafish, the contribution of the individual paralogs to the overall pattern differs between the two teleosts and indicate lineage specific expression shuffling.