Skeletal Muscle Phenotypically Converts and Selectively Inhibits Metastatic Cells in Mice

Ara Parlakian, Iman Gomaa, Sounkary Solly, Ludovic Arandel, Alka Mahale, Gustav Born, Giovanna Marazzi, David Sassoon

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish
Article numbere0009299
JournalPLoS ONE
Volume5
Issue number2
DOIs
StatePublished - 2010
Externally publishedYes

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