Lactic Acidosis Together with GM-CSF and M-CSF Induces Human Macrophages toward an Inflammatory Protumor Phenotype.
Acidosis, Lactic
/ immunology
Cell Differentiation
/ drug effects
Cytokines
/ metabolism
Female
Granulocyte-Macrophage Colony-Stimulating Factor
/ pharmacology
Humans
Inflammation
/ etiology
Macrophage Colony-Stimulating Factor
/ pharmacology
Macrophages
/ drug effects
Monocytes
/ drug effects
Ovarian Neoplasms
/ etiology
Phenotype
Tumor Cells, Cultured
Journal
Cancer immunology research
ISSN: 2326-6074
Titre abrégé: Cancer Immunol Res
Pays: United States
ID NLM: 101614637
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
17
10
2018
revised:
12
07
2019
accepted:
03
01
2020
pubmed:
12
1
2020
medline:
21
10
2020
entrez:
12
1
2020
Statut:
ppublish
Résumé
In established tumors, tumor-associated macrophages (TAM) orchestrate nonresolving cancer-related inflammation and produce mediators favoring tumor growth, metastasis, and angiogenesis. However, the factors conferring inflammatory and protumor properties on human macrophages remain largely unknown. Most solid tumors have high lactate content. We therefore analyzed the impact of lactate on human monocyte differentiation. We report that prolonged lactic acidosis induces the differentiation of monocytes into macrophages with a phenotype including protumor and inflammatory characteristics. These cells produce tumor growth factors, inflammatory cytokines, and chemokines as well as low amounts of IL10. These effects of lactate require its metabolism and are associated with hypoxia-inducible factor-1α stabilization. The expression of some lactate-induced genes is dependent on autocrine M-CSF consumption. Finally, TAMs with protumor and inflammatory characteristics (VEGF
Identifiants
pubmed: 31924656
pii: 2326-6066.CIR-18-0749
doi: 10.1158/2326-6066.CIR-18-0749
doi:
Substances chimiques
CSF2 protein, human
0
Cytokines
0
Macrophage Colony-Stimulating Factor
81627-83-0
Granulocyte-Macrophage Colony-Stimulating Factor
83869-56-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
383-395Informations de copyright
©2020 American Association for Cancer Research.