In vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma

Cancer Cell. 2012 May 15;21(5):680-93. doi: 10.1016/j.ccr.2012.03.043.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Movement*
  • Disease Progression
  • Humans
  • Mice
  • Mice, SCID
  • Microscopy, Confocal
  • Microscopy, Fluorescence, Multiphoton
  • Myogenic Regulatory Factor 5 / genetics
  • Myogenic Regulatory Factor 5 / metabolism
  • Myogenin / genetics
  • Myogenin / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Recombinant Fusion Proteins / metabolism
  • Rhabdomyosarcoma, Embryonal / blood supply
  • Rhabdomyosarcoma, Embryonal / genetics
  • Rhabdomyosarcoma, Embryonal / metabolism
  • Rhabdomyosarcoma, Embryonal / pathology*
  • Time Factors
  • Tumor Cells, Cultured
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • Myogenic Regulatory Factor 5
  • Myogenin
  • Recombinant Fusion Proteins
  • Zebrafish Proteins

Associated data

  • GEO/GSE32425