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 linea...

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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
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cited_by cdi_FETCH-LOGICAL-c725t-85333132b5b517d1359d04e7ce52e7995cd3d37a846ed4c4de1e99fac9f7c0bf3
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creator Parlakian, Ara
Gomaa, Iman
Solly, Sounkary
Arandel, Ludovic
Mahale, Alka
Born, Gustav
Marazzi, Giovanna
Sassoon, David
description 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.
doi_str_mv 10.1371/journal.pone.0009299
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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
title Skeletal muscle phenotypically converts and selectively inhibits metastatic cells in mice
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