Skeletal muscle phenotypically converts and selectively inhibits metastatic cells in mice.
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.
Parlakian
Ara
A
Myology Group, UMR S 787 Inserm, Université Paris VI/Pierre et Marie Curie, Paris, France.
Gomaa
Iman
I
Solly
Sounkary
S
Arandel
Ludovic
L
Mahale
Alka
A
Born
Gustav
G
Marazzi
Giovanna
G
Sassoon
David
D
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
D017077:Culture Media, Conditioned; D003893:Desmin; D008543:Melanins; D049452:Green Fluorescent Proteins