In Vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma
- Authors
- 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.
- ID
- ZDB-PUB-120529-40
- Date
- 2012
- Source
- Cancer Cell 21(5): 680-693 (Journal)
- Registered Authors
- Ignatius, Myron, Langenau, David
- Keywords
- none
- Datasets
- 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.