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The chick embryo neural crest model system reveals a unique role for EphB6 in melanoma metastasis
Author(s) -
Bailey Caleb Michael,
Kulesa Paul M
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.967.1
Subject(s) - neural crest , melanoma , metastasis , biology , embryonic stem cell , cancer research , intravasation , embryo , microbiology and biotechnology , cancer , genetics , gene
We hypothesize that melanoma metastasis mimics aspects of the emigration program of its ancestral cell type, the embryonic neural crest. To test our hypothesis, we performed a molecular comparison between melanoma and the neural crest. Our study revealed that melanoma cells exploit portions of the embryonic neural crest development program to facilitate invasion. In particular, the purported metastasis suppressor EphB6 was reduced in invasive melanoma cells compared to poorly invasive melanoma cells and primary human melanocytes. Thus, we utilized the chick embryo transplant model system to assay the effects of EphB6 re‐expression in melanoma cells. We report that EphB6 over‐expression alters cell directionality of migrating melanoma cells, while also reducing invasive ability. We confirmed the anti‐metastatic effect of EphB6 in melanoma cells using a chick CAM metastasis assay, while tumor formation appeared unaffected. These results suggest that EphB6 acts specifically as a metastasis suppressor, likely at the metastatic step of intravasation. Our studies also demonstrate the chick embryo as a powerful tool with which to compare and dissect the complex mechanisms of metastasis in vivo that are similar or distinct from normal developmental processes. This work was supported by NRSA 1F32CA144297 (cmb) from the NIH, and by the Stowers Institute for Medical Research. Grant Funding Source : NIH 1R01HD057922