In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities.

Although tumor-associated macrophages (TAMs) are involved in tumor growth and metastasis, the mechanisms controlling their pro-tumoral activities remain largely unknown. The transcription factor c-MYC has been recently shown to regulate in vitro human macrophage polarization and be expressed in macr...

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Autores principales:	Oscar M Pello, Raphael Chèvre, Damya Laoui, Alba De Juan, Fidel Lolo, María Jesús Andrés-Manzano, Manuel Serrano, Jo A Van Ginderachter, Vicente Andrés
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/566b08411797436f949519df450ee65b
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spelling	oai:doaj.org-article:566b08411797436f949519df450ee65b2021-11-18T07:04:46ZIn vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities.1932-620310.1371/journal.pone.0045399https://doaj.org/article/566b08411797436f949519df450ee65b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028984/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Although tumor-associated macrophages (TAMs) are involved in tumor growth and metastasis, the mechanisms controlling their pro-tumoral activities remain largely unknown. The transcription factor c-MYC has been recently shown to regulate in vitro human macrophage polarization and be expressed in macrophages infiltrating human tumors. In this study, we exploited the predominant expression of LysM in myeloid cells to generate c-Myc(fl/fl) LysM(cre/+) mice, which lack c-Myc in macrophages, to investigate the role of macrophage c-MYC expression in cancer. Under steady-state conditions, immune system parameters in c-Myc(fl/fl) LysM(cre/+) mice appeared normal, including the abundance of different subsets of bone marrow hematopoietic stem cells, precursors and circulating cells, macrophage density, and immune organ structure. In a model of melanoma, however, TAMs lacking c-Myc displayed a delay in maturation and showed an attenuation of pro-tumoral functions (e.g., reduced expression of VEGF, MMP9, and HIF1α) that was associated with impaired tissue remodeling and angiogenesis and limited tumor growth in c-Myc(fl/fl) LysM(cre/+) mice. Macrophage c-Myc deletion also diminished fibrosarcoma growth. These data identify c-Myc as a positive regulator of the pro-tumoral program of TAMs and suggest c-Myc inactivation as an attractive target for anti-cancer therapy.Oscar M PelloRaphael ChèvreDamya LaouiAlba De JuanFidel LoloMaría Jesús Andrés-ManzanoManuel SerranoJo A Van GinderachterVicente AndrésPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45399 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Oscar M Pello Raphael Chèvre Damya Laoui Alba De Juan Fidel Lolo María Jesús Andrés-Manzano Manuel Serrano Jo A Van Ginderachter Vicente Andrés In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities.
description	Although tumor-associated macrophages (TAMs) are involved in tumor growth and metastasis, the mechanisms controlling their pro-tumoral activities remain largely unknown. The transcription factor c-MYC has been recently shown to regulate in vitro human macrophage polarization and be expressed in macrophages infiltrating human tumors. In this study, we exploited the predominant expression of LysM in myeloid cells to generate c-Myc(fl/fl) LysM(cre/+) mice, which lack c-Myc in macrophages, to investigate the role of macrophage c-MYC expression in cancer. Under steady-state conditions, immune system parameters in c-Myc(fl/fl) LysM(cre/+) mice appeared normal, including the abundance of different subsets of bone marrow hematopoietic stem cells, precursors and circulating cells, macrophage density, and immune organ structure. In a model of melanoma, however, TAMs lacking c-Myc displayed a delay in maturation and showed an attenuation of pro-tumoral functions (e.g., reduced expression of VEGF, MMP9, and HIF1α) that was associated with impaired tissue remodeling and angiogenesis and limited tumor growth in c-Myc(fl/fl) LysM(cre/+) mice. Macrophage c-Myc deletion also diminished fibrosarcoma growth. These data identify c-Myc as a positive regulator of the pro-tumoral program of TAMs and suggest c-Myc inactivation as an attractive target for anti-cancer therapy.
format	article
author	Oscar M Pello Raphael Chèvre Damya Laoui Alba De Juan Fidel Lolo María Jesús Andrés-Manzano Manuel Serrano Jo A Van Ginderachter Vicente Andrés
author_facet	Oscar M Pello Raphael Chèvre Damya Laoui Alba De Juan Fidel Lolo María Jesús Andrés-Manzano Manuel Serrano Jo A Van Ginderachter Vicente Andrés
author_sort	Oscar M Pello
title	In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities.
title_short	In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities.
title_full	In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities.
title_fullStr	In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities.
title_full_unstemmed	In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities.
title_sort	in vivo inhibition of c-myc in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/566b08411797436f949519df450ee65b
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In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities.

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