Myogenic Cell Proliferation and Generation of a Reversible Tumorigenic Phenotype Are Triggered by Preirradiation of the Recipient Site

• Published in: The Journal of cell biology 2002-05, Vol.157 (4), p.693-702
• Main Authors: Morgan, Jennifer E., Gross, Jacqueline G., Pagel, Charles N., Beauchamp, Jonathan R., Fassati, Ariberto, Thrasher, Adrian J., Di Santo, James P., Fisher, Ivan B., Shiwen, Xu, Abraham, David J., Partridge, Terence A.
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - physiology; Cell Differentiation - radiation effects; Cell Division - physiology; Cell Division - radiation effects; Cell growth; Cell Line, Transformed; Cell lines; Cell Movement - drug effects; Cell Movement - physiology; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Cell Transformation, Neoplastic - radiation effects; Cells; Clone Cells - cytology; Clone Cells - metabolism; Clone Cells - radiation effects; Dystrophin - deficiency; Dystrophin - genetics; Graft Survival - physiology; Graft Survival - radiation effects; Interstitial cells; Irradiation; Legs; Male; Mice; Mice, Inbred mdx; Muscle, Skeletal - cytology; Muscle, Skeletal - growth & development; Muscle, Skeletal - radiation effects; Muscles; Muscular system; Neoplasms, Radiation-Induced - metabolism; Neoplasms, Radiation-Induced - pathology; Neoplasms, Radiation-Induced - physiopathology; Phenotype; Radiation; Regeneration - physiology; Regeneration - radiation effects; Rodents; Skeletal muscle satellite cells; Stem Cell Transplantation; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Tissue Transplantation; Tumors
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200108047

Environmental influences have profound yet reversible effects on the behavior of resident cells. Earlier data have indicated that the amount of muscle formed from implanted myogenic cells is greatly augmented by prior irradiation (18 Gy) of the host mouse muscle. Here we confirm this phenomenon, showing that it varies between host mouse strains. However, it is unclear whether it is due to secretion of proliferative factors or reduction of anti-proliferative agents. To investigate this further, we have exploited the observation that the immortal myogenic C2 C12 cell line forms tumors far more rapidly in irradiated than in nonirradiated host muscle. We show that the effect of preirradiation on tumor formation is persistent and dose dependent. However, C2 C12 cells are not irreversibly compelled to form undifferentiated tumor cells by the irradiated muscle environment and are still capable of forming large amounts of muscle when reimplanted into a nonirradiated muscle. In a clonal analysis of this effect, we discovered that C2 C12 cells have a bimodal propensity to form tumors; some clones form no tumors even after extensive periods in irradiated graft sites, whereas others rapidly form extensive tumors. This illustrates the subtle interplay between the phenotype of implanted cells and the factors in the muscle environment.