title: In vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma.
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.
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA.
authors.forename: Myron S
authors.initials: MS
authors.lastname: Ignatius
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Chen
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129, USA.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Elpek
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA.
authors.forename: Adam Z
authors.initials: AZ
authors.lastname: Fuller
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA; Instituto de Ciências Biomédicas Abel Salazar, 4099-003 Porto, Portugal.
authors.forename: Inês M
authors.initials: IM
authors.lastname: Tenente
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Clagg
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA.
authors.forename: Sali
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Blackburn
authors.affiliation: Departments of Pediatrics, Pharmacology, and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Linardic
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Rosenberg
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA.
authors.forename: Petur G
authors.initials: PG
authors.lastname: Nielsen
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129, USA.
authors.forename: Thorsten R
authors.initials: TR
authors.lastname: Mempel
authors.affiliation: Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA. Electronic address: dlangenau@partners.org.
authors.forename: David M
authors.initials: DM
authors.lastname: Langenau
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D018450:Disease Progression; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D018613:Microscopy, Confocal; D036641:Microscopy, Fluorescence, Multiphoton; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D018233:Rhabdomyosarcoma, Embryonal / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D011993:Recombinant Fusion Proteins; D029961:Zebrafish Proteins