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Increased Arginase1 expression in tumor microenvironment promotes mammary carcinogenesis via multiple mechanisms.
- Source :
-
Carcinogenesis [Carcinogenesis] 2020 Dec 31; Vol. 41 (12), pp. 1695-1702. - Publication Year :
- 2020
-
Abstract
- Arginine metabolism plays a significant role in regulating cell function, affecting tumor growth and metastatization. To study the effect of the arginine-catabolizing enzyme Arginase1 (ARG1) on tumor microenvironment, we generated a mouse model of mammary carcinogenesis by crossbreeding a transgenic mouse line overexpressing ARG1 in macrophages (FVBArg+/+) with the MMTV-Neu mouse line (FVBNeu+/+). This double transgenic line (FVBArg+/-;Neu+/+) showed a significant shortening in mammary tumor latency, and an increase in the number of mammary nodules. Transfer of tumor cells from FVBNeu+/+ into either FVB wild type or FVBArg+/+ mice resulted in increase regulatory T cells in the tumor infiltrate, suggestive of an impaired antitumor immune response. However, we also found increased frequency of tumor stem cells in tumors from FVBArg+/-;Neu+/+ transgenic compared with FVBNeu+/+ mice, suggesting that increased arginine metabolism in mammary tumor microenvironment may supports the cancer stem cells niche. We provide in vivo evidence of a novel, yet unexploited, mechanism through which ARG1 may contribute to tumor development.<br /> (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Animals
Apoptosis
Arginase genetics
Cell Proliferation
Cell Transformation, Neoplastic genetics
Cell Transformation, Neoplastic immunology
Cell Transformation, Neoplastic metabolism
Female
Humans
Mammary Neoplasms, Experimental genetics
Mammary Neoplasms, Experimental immunology
Mammary Neoplasms, Experimental metabolism
Mice
Mice, Transgenic
Tumor Cells, Cultured
Arginase metabolism
Cell Transformation, Neoplastic pathology
Mammary Neoplasms, Experimental pathology
Tumor Microenvironment immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2180
- Volume :
- 41
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 32614387
- Full Text :
- https://doi.org/10.1093/carcin/bgaa063