In Vivo Imaging of Tumor-Propagating Cells, Regional Tumor Heterogeneity, and Dynamic Cell Movements in Embryonal Rhabdomyosarcoma

Myron S. Ignatius, Eleanor Chen, Natalie M. Elpek, Adam Z. Fuller, Inês M. Tenente, Ryan Clagg, Sali Liu, Jessica S. Blackburn, Corinne M. Linardic, Andrew E. Rosenberg, Petur G. Nielsen, Thorsten R. Mempel, David M. Langenau

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

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.

Original languageEnglish
Pages (from-to)680-693
Number of pages14
JournalCancer Cell
Volume21
Issue number5
DOIs
StatePublished - May 25 2012

Bibliographical note

Funding Information:
E.C. and J.S.B. are supported by the National Institutes of Health (NIH) Training Grants T32 HL007627 and 5T32CA09216-26, respectively. C.M.L. is supported by R01 CA122706 and K12 HD043494. D.M.L. is supported by NIH Grants K01 AR055619, 1RO1CA154923, and 1R21CA156056; the Alex's Lemonade Stand Foundation; the Sarcoma Foundation of America; the American Cancer Society; and the Harvard Stem Cell Institute. I.M.T. is supported by Fundação para a Ciência e Tecnologia (the Portuguese Foundation for Science and Technology) through Fellowship SFRH/BD/51288/2010. We thank Huai-Jen Tsai for myf5-GFP transgenic animals and Clarrisa Henry for critical review of our manuscript.

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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