2026-06-30T03:03:17Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/76652024-09-27T08:27:27Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Pello, Oscar M
author
Chevre, Raphael
author
Laoui, Damya
author
De Juan, Alba
author
Lolo, Fidel Nicolas
author
Andres-Manzano, Maria J.
author
Serrano, Manuel
author
Van Ginderachter, Jo A
author
Andres, Vicente
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea. Comisión Europea
funder
Fundación ProCNIC
2019-05-23T10:06:18Z
2019-05-23T10:06:18Z
2012
PLoS One. 2012; 7(9):e45399
10.1371/journal.pone.0045399
1932-6203
1932-6203
PloS one
23028984
http://hdl.handle.net/20.500.12105/7665
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.
eng
In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities
journal article
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InVivoInhibitionofc-MYC_2012.pdf
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InVivoInhibitionofc-MYC_2012.pdf.txt