Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pello, Oscar M., Chèvre, Raphael, Laoui, Damya, De Juan, Alba, Lolo, Fidel, Andrés-Manzano, María Jesús, Serrano, Manuel, Van Ginderachter, Jo A., Andrés, Vicente
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447925/
https://www.ncbi.nlm.nih.gov/pubmed/23028984
http://dx.doi.org/10.1371/journal.pone.0045399
_version_ 1782244196579540992
author Pello, Oscar M.
Chèvre, Raphael
Laoui, Damya
De Juan, Alba
Lolo, Fidel
Andrés-Manzano, María Jesús
Serrano, Manuel
Van Ginderachter, Jo A.
Andrés, Vicente
author_facet Pello, Oscar M.
Chèvre, Raphael
Laoui, Damya
De Juan, Alba
Lolo, Fidel
Andrés-Manzano, María Jesús
Serrano, Manuel
Van Ginderachter, Jo A.
Andrés, Vicente
author_sort Pello, Oscar M.
collection PubMed
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 Online
Article
Text
id pubmed-3447925
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-34479252012-10-01 In Vivo Inhibition of c-MYC in Myeloid Cells Impairs Tumor-Associated Macrophage Maturation and Pro-Tumoral Activities Pello, Oscar M. Chèvre, Raphael Laoui, Damya De Juan, Alba Lolo, Fidel Andrés-Manzano, María Jesús Serrano, Manuel Van Ginderachter, Jo A. Andrés, Vicente PLoS One Research Article 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. Public Library of Science 2012-09-20 /pmc/articles/PMC3447925/ /pubmed/23028984 http://dx.doi.org/10.1371/journal.pone.0045399 Text en © 2012 Pello et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pello, Oscar M.
Chèvre, Raphael
Laoui, Damya
De Juan, Alba
Lolo, Fidel
Andrés-Manzano, María Jesús
Serrano, Manuel
Van Ginderachter, Jo A.
Andrés, Vicente
In Vivo Inhibition of c-MYC in Myeloid Cells Impairs Tumor-Associated Macrophage Maturation and Pro-Tumoral Activities
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447925/
https://www.ncbi.nlm.nih.gov/pubmed/23028984
http://dx.doi.org/10.1371/journal.pone.0045399
work_keys_str_mv AT pellooscarm invivoinhibitionofcmycinmyeloidcellsimpairstumorassociatedmacrophagematurationandprotumoralactivities
AT chevreraphael invivoinhibitionofcmycinmyeloidcellsimpairstumorassociatedmacrophagematurationandprotumoralactivities
AT laouidamya invivoinhibitionofcmycinmyeloidcellsimpairstumorassociatedmacrophagematurationandprotumoralactivities
AT dejuanalba invivoinhibitionofcmycinmyeloidcellsimpairstumorassociatedmacrophagematurationandprotumoralactivities
AT lolofidel invivoinhibitionofcmycinmyeloidcellsimpairstumorassociatedmacrophagematurationandprotumoralactivities
AT andresmanzanomariajesus invivoinhibitionofcmycinmyeloidcellsimpairstumorassociatedmacrophagematurationandprotumoralactivities
AT serranomanuel invivoinhibitionofcmycinmyeloidcellsimpairstumorassociatedmacrophagematurationandprotumoralactivities
AT vanginderachterjoa invivoinhibitionofcmycinmyeloidcellsimpairstumorassociatedmacrophagematurationandprotumoralactivities
AT andresvicente invivoinhibitionofcmycinmyeloidcellsimpairstumorassociatedmacrophagematurationandprotumoralactivities