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Angiotensin II drives the production of tumor-promoting macrophages.
- Source :
-
Immunity [Immunity] 2013 Feb 21; Vol. 38 (2), pp. 296-308. Date of Electronic Publication: 2013 Jan 17. - Publication Year :
- 2013
-
Abstract
- 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.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Adenocarcinoma genetics
Adenocarcinoma pathology
Adenocarcinoma of Lung
Angiotensin II metabolism
Animals
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung pathology
Cell Communication
Cell Movement
Cell Proliferation
Gene Expression
Hematopoietic Stem Cells metabolism
Hematopoietic Stem Cells pathology
Humans
Lung Neoplasms genetics
Lung Neoplasms pathology
Lysophospholipids metabolism
Macrophages pathology
Mice
Mice, Transgenic
Signal Transduction
Sphingosine analogs & derivatives
Sphingosine metabolism
Spleen pathology
Tumor Burden
Adenocarcinoma metabolism
Angiotensin II genetics
Carcinoma, Non-Small-Cell Lung metabolism
Lung Neoplasms metabolism
Macrophages metabolism
Spleen metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 38
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 23333075
- Full Text :
- https://doi.org/10.1016/j.immuni.2012.10.015