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

doi:10.1016/j.ccr.2012.03.043

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 journal › Article › peer-review

82 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 language	English (US)
Pages (from-to)	680-693
Number of pages	14
Journal	Cancer Cell
Volume	21
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2012.03.043
State	Published - May 25 2012
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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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., & Langenau, D. M. (2012). In Vivo Imaging of Tumor-Propagating Cells, Regional Tumor Heterogeneity, and Dynamic Cell Movements in Embryonal Rhabdomyosarcoma. Cancer Cell, 21(5), 680-693. https://doi.org/10.1016/j.ccr.2012.03.043

In Vivo Imaging of Tumor-Propagating Cells, Regional Tumor Heterogeneity, and Dynamic Cell Movements in Embryonal Rhabdomyosarcoma. / Ignatius, Myron S.; Chen, Eleanor; Elpek, Natalie M.; Fuller, Adam Z.; Tenente, Inês M.; Clagg, Ryan; Liu, Sali; Blackburn, Jessica S.; Linardic, Corinne M.; Rosenberg, Andrew E.; Nielsen, Petur G.; Mempel, Thorsten R.; Langenau, David M.

In: Cancer Cell, Vol. 21, No. 5, 25.05.2012, p. 680-693.

Research output: Contribution to journal › Article › peer-review

Ignatius, MS, Chen, E, Elpek, NM, Fuller, AZ, Tenente, IM, Clagg, R, Liu, S, Blackburn, JS, Linardic, CM, Rosenberg, AE, Nielsen, PG, Mempel, TR & Langenau, DM 2012, 'In Vivo Imaging of Tumor-Propagating Cells, Regional Tumor Heterogeneity, and Dynamic Cell Movements in Embryonal Rhabdomyosarcoma', Cancer Cell, vol. 21, no. 5, pp. 680-693. https://doi.org/10.1016/j.ccr.2012.03.043

Ignatius, Myron S. ; Chen, Eleanor ; Elpek, Natalie M. ; Fuller, Adam Z. ; Tenente, Inês M. ; Clagg, Ryan ; Liu, Sali ; Blackburn, Jessica S. ; Linardic, Corinne M. ; Rosenberg, Andrew E. ; Nielsen, Petur G. ; Mempel, Thorsten R. ; Langenau, David M. / In Vivo Imaging of Tumor-Propagating Cells, Regional Tumor Heterogeneity, and Dynamic Cell Movements in Embryonal Rhabdomyosarcoma. In: Cancer Cell. 2012 ; Vol. 21, No. 5. pp. 680-693.

@article{07066017968e4b64afd56d82d6325f4a,

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.",

author = "Ignatius, {Myron S.} and Eleanor Chen and Elpek, {Natalie M.} and Fuller, {Adam Z.} and Tenente, {In{\^e}s M.} and Ryan Clagg and Sali Liu and Blackburn, {Jessica S.} and Linardic, {Corinne M.} and Rosenberg, {Andrew E.} and Nielsen, {Petur G.} and Mempel, {Thorsten R.} and Langenau, {David M.}",

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 Funda{\c c}{\~a}o para a Ci{\^e}ncia 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. ",

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AU - Ignatius, Myron S.

AU - Chen, Eleanor

AU - Elpek, Natalie M.

AU - Fuller, Adam Z.

AU - Tenente, Inês M.

AU - Clagg, Ryan

AU - Liu, Sali

AU - Blackburn, Jessica S.

AU - Linardic, Corinne M.

AU - Rosenberg, Andrew E.

AU - Nielsen, Petur G.

AU - Mempel, Thorsten R.

AU - Langenau, David M.

N1 - 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.

PY - 2012/5/25

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N2 - 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.

AB - 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.

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