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Comprehensive Proteomics Analysis Reveals Metabolic Reprogramming of Tumor-Associated Macrophages Stimulated by the Tumor Microenvironment.
- Source :
-
Journal of proteome research [J Proteome Res] 2017 Jan 06; Vol. 16 (1), pp. 288-297. Date of Electronic Publication: 2016 Nov 03. - Publication Year :
- 2017
-
Abstract
- Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment. Although a role for TAMs in promoting tumor progression has been revealed, the differentiation mechanisms and intrinsic signals of TAMs regulated by the tumor microenvironment remain unclear. Here we constructed an in vitro TAMs cell model, TES-TAMs, which is from tumor-extract-stimulated bone-marrow-derived macrophages. We performed a comparative proteomics analysis of bone-marrow-derived macrophages and TES-TAMs, which indicated that TES-TAMs possessed characteristic molecular expression of TAMs. Intriguingly, the signal pathways enriched in up-regulated differentially expressed proteins of TAMs demonstrated that glycolysis metabolism reprogramming may play an important role in TAM differentiation. We found that hexokinase-2, a key mediator of aerobic glycolysis, and the downstream proteins PFKL and ENO1 were remarkably increased in both TES-TAMs and primary TAMs from our MMTV-PyMT mice model. This phenomenon was then verified in human THP-1 cell lines stimulated by tumor extract solution from breast cancer patient. Taken together, our study provides insight into the induction of TAM differentiation by the tumor microenvironment through metabolic reprogramming.
- Subjects :
- Animals
Cell Differentiation
Complex Mixtures pharmacology
Cytokines genetics
Cytokines metabolism
Female
Hexokinase genetics
Hexokinase metabolism
Humans
Macrophages metabolism
Macrophages pathology
Mammary Neoplasms, Experimental metabolism
Mammary Neoplasms, Experimental pathology
Metabolic Networks and Pathways genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Proteome metabolism
Signal Transduction
Tumor Burden
Cellular Reprogramming drug effects
Gene Expression Regulation, Neoplastic
Macrophages drug effects
Mammary Neoplasms, Experimental genetics
Metabolic Networks and Pathways drug effects
Proteome genetics
Tumor Microenvironment genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1535-3907
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of proteome research
- Publication Type :
- Academic Journal
- Accession number :
- 27809537
- Full Text :
- https://doi.org/10.1021/acs.jproteome.6b00604