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A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation).
- Source :
-
Blood [Blood] 2006 Mar 01; Vol. 107 (5), pp. 2112-22. Date of Electronic Publication: 2005 Nov 03. - Publication Year :
- 2006
-
Abstract
- To identify the molecular basis underlying the functions of tumor-associated macrophages (TAMs), we characterized the gene expression profile of TAMs isolated from a murine fibrosarcoma in comparison with peritoneal macrophages (PECs) and myeloid suppressor cells (MSCs), using a cDNA microarray technology. Among the differentially expressed genes, 15 genes relevant to inflammation and immunity were validated by real-time polymerase chain reaction (PCR) and protein production. Resting TAMs showed a characteristic gene expression pattern with higher expression of genes coding for the immunosuppressive cytokine IL-10, phagocytosis-related receptors/molecules (Msr2 and C1q), and inflammatory chemokines (CCL2 and CCL5) as expected, as well as, unexpectedly, IFN-inducible chemokines (CXCL9, CXCL10, CXCL16). Immunohistology confirmed and extended the in vitro analysis by showing that TAMs express M2-associated molecules (eg, IL-10 and MGL1), as well as CCL2, CCL5, CXCL9, CXCL10, and CXCL16, but no appreciable NOS2. Lipopolysaccharide (LPS)-mediated activation of TAMs resulted in defective expression of several proinflammatory cytokines (eg, IL-1beta, IL-6, TNF-alpha) and chemokines (eg, CCL3), as opposed to a strong up-regulation of immunosuppressive cytokines (IL-10, TGFbeta) and IFN-inducible chemokines (CCL5, CXCL9, CXCL10, CXCL16). Thus, profiling of TAMs from a murine sarcoma revealed unexpected expression of IFN-inducible chemokines, associated with an M2 phenotype (IL-10high, IL-12low), and divergent regulation of the NF-kappaB versus the IRF-3/STAT1 pathway.
- Subjects :
- Animals
Cell Line, Tumor
Fibrosarcoma pathology
Gene Expression Profiling
Humans
Immunohistochemistry
Macrophages pathology
Male
Mice
Neoplasm Transplantation
Neoplasms, Experimental metabolism
Neoplasms, Experimental pathology
Oligonucleotide Array Sequence Analysis
Phagocytosis
Signal Transduction
Fibrosarcoma metabolism
Gene Expression Regulation, Neoplastic
Interferon Regulatory Factor-3 metabolism
Macrophages metabolism
NF-kappa B metabolism
STAT1 Transcription Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 107
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 16269622
- Full Text :
- https://doi.org/10.1182/blood-2005-01-0428