ZFIN ID: ZDB-PUB-120529-40
In Vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma
Ignatius, M.S., Chen, E., Elpek, N.M., Fuller, A.Z., Tenente, I.M., Clagg, R., Liu, S., Blackburn, J.S., Linardic, C.M., Rosenberg, A.E., Nielsen, P.G., Mempel, T.R., and Langenau, D.M.
Date: 2012
Source: Cancer Cell   21(5): 680-693 (Journal)
Registered Authors: Ignatius, Myron, Langenau, David
Keywords: none
Microarrays: GEO:GSE32425
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
PubMed: 22624717 Full text @ Cancer Cell

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.