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Angiotensin II Drives the Production of Tumor-Promoting Macrophages
- Source :
- Immunity. 38(2):296-308
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- Summary Macrophages frequently infiltrate tumors and can enhance cancer growth, yet the origins of the macrophage response are not well understood. Here we address molecular mechanisms of macrophage production in a conditional mouse model of lung adenocarcinoma. We report that overproduction of the peptide hormone Angiotensin II (AngII) in tumor-bearing mice amplifies self-renewing hematopoietic stem cells (HSCs) and macrophage progenitors. The process occurred in the spleen but not the bone marrow, and was independent of hemodynamic changes. The effects of AngII required direct hormone ligation on HSCs, depended on S1P 1 signaling, and allowed the extramedullary tissue to supply new tumor-associated macrophages throughout cancer progression. Conversely, blocking AngII production prevented cancer-induced HSC and macrophage progenitor amplification and thus restrained the macrophage response at its source. These findings indicate that AngII acts upstream of a potent macrophage amplification program and that tumors can remotely exploit the hormone's pathway to stimulate cancer-promoting immunity.
- Subjects :
- Cell signaling
Lung Neoplasms
Immunology
Gene Expression
Adenocarcinoma of Lung
Mice, Transgenic
Cell Communication
Adenocarcinoma
Biology
Mice
03 medical and health sciences
0302 clinical medicine
Cell Movement
Sphingosine
Carcinoma, Non-Small-Cell Lung
medicine
Animals
Humans
Macrophage
Immunology and Allergy
Progenitor cell
Cell Proliferation
030304 developmental biology
0303 health sciences
Angiotensin II
Macrophages
Hematopoietic Stem Cells
Tumor Burden
Haematopoiesis
medicine.anatomical_structure
Infectious Diseases
030220 oncology & carcinogenesis
Cancer research
Bone marrow
Lysophospholipids
Signal transduction
Stem cell
Spleen
Signal Transduction
Subjects
Details
- ISSN :
- 10747613
- Volume :
- 38
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Immunity
- Accession number :
- edsair.doi.dedup.....24ee448cafc1fdc4277302931f8bbb75
- Full Text :
- https://doi.org/10.1016/j.immuni.2012.10.015