title: Skeletal muscle phenotypically converts and selectively inhibits metastatic cells in mice.
abstract: 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.
authors.affiliation: Myology Group, UMR S 787 Inserm, Université Paris VI/Pierre et Marie Curie, Paris, France.
authors.forename: Ara
authors.initials: A
authors.lastname: Parlakian
authors.forename: Iman
authors.initials: I
authors.lastname: Gomaa
authors.forename: Sounkary
authors.initials: S
authors.lastname: Solly
authors.forename: Ludovic
authors.initials: L
authors.lastname: Arandel
authors.forename: Alka
authors.initials: A
authors.lastname: Mahale
authors.forename: Gustav
authors.initials: G
authors.lastname: Born
authors.forename: Giovanna
authors.initials: G
authors.lastname: Marazzi
authors.forename: David
authors.initials: D
authors.lastname: Sassoon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003893:Desmin / Q000235:genetics / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008543:Melanins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017077:Culture Media, Conditioned; D003893:Desmin; D008543:Melanins; D049452:Green Fluorescent Proteins