Tumor cells of the muscle-related
cancer alveolar rhabdomyosarcoma (aRMS) have dysregulated terminal myogenic 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 myoblasts. 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 allograft 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.