Abstract
Embryonal rhabdomyosarcoma (ERMS) is an aggressive pediatric sarcoma of muscle. Here, we show that ERMS-propagating potential is confined to myf5+ cells and can be visualized in live, fluorescent transgenic zebrafish. During early tumor growth, myf5+ ERMS cells reside adjacent normal muscle fibers. By late-stage ERMS, myf5+ cells are reorganized into distinct regions separated from differentiated tumor cells. Time-lapse imaging of late-stage ERMS revealed that myf5+ cells populate newly formed tumor only after seeding by highly migratory myogenin+ ERMS cells. Moreover, myogenin+ ERMS cells can enter the vasculature, whereas myf5+ ERMS-propagating cells do not. Our data suggest that non-tumor-propagating cells likely have important supportive roles in cancer progression and facilitate metastasis.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Video-Audio Media
MeSH terms
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Animals
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Animals, Genetically Modified
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism
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Cell Movement*
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Disease Progression
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Humans
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Mice
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Mice, SCID
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Microscopy, Confocal
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Microscopy, Fluorescence, Multiphoton
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Myogenic Regulatory Factor 5 / genetics
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Myogenic Regulatory Factor 5 / metabolism
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Myogenin / genetics
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Myogenin / metabolism
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Neoplasm Invasiveness
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Neoplasm Transplantation
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / pathology
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Recombinant Fusion Proteins / metabolism
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Rhabdomyosarcoma, Embryonal / blood supply
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Rhabdomyosarcoma, Embryonal / genetics
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Rhabdomyosarcoma, Embryonal / metabolism
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Rhabdomyosarcoma, Embryonal / pathology*
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Time Factors
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Tumor Cells, Cultured
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Zebrafish / genetics
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism
Substances
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Biomarkers, Tumor
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Myogenic Regulatory Factor 5
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Myogenin
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Recombinant Fusion Proteins
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Zebrafish Proteins