Skeletal muscle phenotypically converts and selectively inhibits metastatic cells in mice

• Published in: PloS one 2010-02, Vol.5 (2), p.e9299-e9299
• Main Authors: Parlakian, Ara, Gomaa, Iman, Solly, Sounkary, Arandel, Ludovic, Mahale, Alka, Born, Gustav, Marazzi, Giovanna, Sassoon, David
• Format: Article
• Language: English
• Subjects: Acids; Adenosine; Angiogenesis; Animals; Apoptosis; Apoptosis - drug effects; Cell Biology; Cell Biology/Cell Signaling; Cell Biology/Cellular Death and Stress Responses; Cell culture; Cell cycle; Cell Differentiation; Cell growth; Cell Line; Cell Line, Tumor; Cell Lineage; Cells, Cultured; Chemical compounds; Coculture Techniques; Culture Media, Conditioned - pharmacology; Cytotoxicity; Cytotoxicity, Immunologic - immunology; Desmin - genetics; Desmin - metabolism; Developmental Biology/Aging; Developmental Biology/Stem Cells; Female; Free radicals; Gene regulation; Genes; Green Fluorescent Proteins - metabolism; Humans; Immunohistochemistry; Life Sciences; Melanin; Melanins - metabolism; Melanoma; Metastases; Metastasis; Mice; Mice, Inbred C57BL; Microphthalmia-associated transcription factor; Microscopy, Confocal; Molecular Biology; Muscle, Skeletal - cytology; Muscle, Skeletal - immunology; Muscle, Skeletal - metabolism; Musculoskeletal system; Myoblasts - cytology; Myoblasts - immunology; Myoblasts - metabolism; Neoplasm Metastasis; Neoplasms, Experimental - immunology; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Oncology; Pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Senescence; Skeletal muscle; Skin cancer; Stem cells; Transcription factors; Tumor suppressor genes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009299

Skeletal muscle is rarely a site of malignant metastasis; the molecular and cellular basis for this rarity is not understood. We report that myogenic cells exert pronounced effects upon co-culture with metastatic melanoma (B16-F10) or carcinoma (LLC1) cells including conversion to the myogenic lineage in vitro and in vivo, as well as inhibition of melanin production in melanoma cells coupled with cytotoxic and cytostatic effects. No effect is seen with non-tumorigenic cells. Tumor suppression assays reveal that the muscle-mediated tumor suppressor effects do not generate resistant clones but function through the down-regulation of the transcription factor MiTF, a master regulator of melanocyte development and a melanoma oncogene. Our findings point to skeletal muscle as a source of therapeutic agents in the treatment of metastatic cancers.