IL-4 receptor blockade abrogates satellite cell: Rhabdomyosarcoma fusion and prevents tumor establishment

Guangheng Li, Ken Kikuchi, Megan Radka, Jinu Abraham, Brian P. Rubin, Charles Keller

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Tumor cells of the muscle-related cancer alveolar rhab-domyosarcoma (aRMS) have dysregulated terminal myo-genic differentiation that is characterized by continuous proliferation, decreased capacity to express markers of terminal differentiation, and inability of tumor cells to fuse to one another in the manner seen for normal myo-blasts. Whether aRMS tumor cells can fuse with normal myogenic progenitors such as skeletal muscle stem cells (satellite cells) or myoblasts is unknown, as is the biological effect of fusion events if the phenomenon occurs. To study this possibility, we isolated primary satellite cells harboring a lacZ Cre-LoxP reporter gene for coculture with murine aRMS primary tumor cells expressing Cre. Results of in vitro and in vivo experiments demonstrated tumor cell - muscle cell progenitor fusion events as well as accelerated rates of tumor establishment and progression when satellite cells and derived muscle progenitors were coinjected with tumor cells in an orthotopic allo-graft model. Interleukin 4 receptor (IL-4R) blocking antibody treatment reversed fusion events in vitro and blocked tumor initiation and progression in vivo. Taken together, this study supports a potential role of tumor cell - host cell fusion and the strong therapeutic potential of IL-4R blockade to prevent the establishment of RMS tumors at new anatomical sites.

Original languageEnglish (US)
Pages (from-to)2304-2312
Number of pages9
JournalStem Cells
Volume31
Issue number11
DOIs
StatePublished - Nov 25 2013

Keywords

  • Fusion
  • IL-4
  • Rhabdomyosarcoma
  • Satellite cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Li, G., Kikuchi, K., Radka, M., Abraham, J., Rubin, B. P., & Keller, C. (2013). IL-4 receptor blockade abrogates satellite cell: Rhabdomyosarcoma fusion and prevents tumor establishment. Stem Cells, 31(11), 2304-2312. https://doi.org/10.1002/stem.1491