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

Molecular and Cellular Biochemistry

Research output: Contribution to journal › Article › peer-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 language	English
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

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.

Funding

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.

Funders	Funder number
Fundação para a Ciência e Tecnologia I.P.
National Institutes of Health (NIH)	K12 HD043494, T32 HL007627, 1RO1CA154923, K01 AR055619, 1R21CA156056, 5T32CA09216-26, R01 CA122706
American Cancer Society-Michigan Cancer Research Fund
National Childhood Cancer Registry – National Cancer Institute	R01CA150975
Alex's Lemonade Stand Foundation for Childhood Cancer
Sarcoma Foundation of America
Harvard Stem Cell Institute
Fundação para a Ciência e Tecnologia I.P.	SFRH/BD/51288/2010

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccr.2012.03.043

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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

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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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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

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T1 - In Vivo Imaging of Tumor-Propagating Cells, Regional Tumor Heterogeneity, and Dynamic Cell Movements in Embryonal Rhabdomyosarcoma

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

Y1 - 2012/5/25

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

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

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