Immunological and Nonimmunological Effects of Indoleamine 2,3-Dioxygenase on Breast Tumor Growth and Spontaneous Metastasis Formation

The role of the tryptophan-catabolizing enzyme, indoleamine 2,3-dioxygenase (IDO1), in tumor escape and metastasis formation was analyzed using two pairs of Ido1+ and Ido1− murine breast cancer cell lines. Ido1 expression in 4T1 cells was knocked down by shRNA, and Ido1 expression in NT-5 cells was...

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Main Authors: Vera Levina, Yunyun Su, Elieser Gorelik
Format: Article
Language:English
Published: Hindawi Limited 2012-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2012/173029
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spelling doaj-2bd2379f90d64ad980667f1ce457a5042020-11-24T22:21:02ZengHindawi LimitedClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/173029173029Immunological and Nonimmunological Effects of Indoleamine 2,3-Dioxygenase on Breast Tumor Growth and Spontaneous Metastasis FormationVera Levina0Yunyun Su1Elieser Gorelik2Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USADepartment of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USADepartment of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USAThe role of the tryptophan-catabolizing enzyme, indoleamine 2,3-dioxygenase (IDO1), in tumor escape and metastasis formation was analyzed using two pairs of Ido1+ and Ido1− murine breast cancer cell lines. Ido1 expression in 4T1 cells was knocked down by shRNA, and Ido1 expression in NT-5 cells was upregulated by stable transfection. Growth of Ido1− tumors and spontaneous metastasis formation were inhibited in immunocompetent mice. A higher level of cytotoxic T lymphocytes was generated by spleen cells from mice bearing Ido1− tumors than Ido1+ tumors. Tumor and metastatic growth was enhanced in immunodeficient mice, confirming an intensified immune response in the absence of Ido1 expression. However, Ido1+ tumors grow faster than Ido1− tumors in immunodeficient SCID/beige mice (lacking T, B, and NK cells) suggesting that some Ido1-controlled nonimmunological mechanisms may be involved in tumor cell growth regulation. In vitro experiments demonstrated that downregulation of Ido1 in tumor cells was associated with decreased cell proliferation, increased apoptosis, and changed expression of cell cycle regulatory genes, whereas upregulation of Ido1 in the cells had the opposite effects. Taken together, our findings indicate that Ido1 expression could exert immunological and nonimmunological effects in murine breast tumor cells.http://dx.doi.org/10.1155/2012/173029
collection DOAJ
language English
format Article
sources DOAJ
author Vera Levina
Yunyun Su
Elieser Gorelik
spellingShingle Vera Levina
Yunyun Su
Elieser Gorelik
Immunological and Nonimmunological Effects of Indoleamine 2,3-Dioxygenase on Breast Tumor Growth and Spontaneous Metastasis Formation
Clinical and Developmental Immunology
author_facet Vera Levina
Yunyun Su
Elieser Gorelik
author_sort Vera Levina
title Immunological and Nonimmunological Effects of Indoleamine 2,3-Dioxygenase on Breast Tumor Growth and Spontaneous Metastasis Formation
title_short Immunological and Nonimmunological Effects of Indoleamine 2,3-Dioxygenase on Breast Tumor Growth and Spontaneous Metastasis Formation
title_full Immunological and Nonimmunological Effects of Indoleamine 2,3-Dioxygenase on Breast Tumor Growth and Spontaneous Metastasis Formation
title_fullStr Immunological and Nonimmunological Effects of Indoleamine 2,3-Dioxygenase on Breast Tumor Growth and Spontaneous Metastasis Formation
title_full_unstemmed Immunological and Nonimmunological Effects of Indoleamine 2,3-Dioxygenase on Breast Tumor Growth and Spontaneous Metastasis Formation
title_sort immunological and nonimmunological effects of indoleamine 2,3-dioxygenase on breast tumor growth and spontaneous metastasis formation
publisher Hindawi Limited
series Clinical and Developmental Immunology
issn 1740-2522
1740-2530
publishDate 2012-01-01
description The role of the tryptophan-catabolizing enzyme, indoleamine 2,3-dioxygenase (IDO1), in tumor escape and metastasis formation was analyzed using two pairs of Ido1+ and Ido1− murine breast cancer cell lines. Ido1 expression in 4T1 cells was knocked down by shRNA, and Ido1 expression in NT-5 cells was upregulated by stable transfection. Growth of Ido1− tumors and spontaneous metastasis formation were inhibited in immunocompetent mice. A higher level of cytotoxic T lymphocytes was generated by spleen cells from mice bearing Ido1− tumors than Ido1+ tumors. Tumor and metastatic growth was enhanced in immunodeficient mice, confirming an intensified immune response in the absence of Ido1 expression. However, Ido1+ tumors grow faster than Ido1− tumors in immunodeficient SCID/beige mice (lacking T, B, and NK cells) suggesting that some Ido1-controlled nonimmunological mechanisms may be involved in tumor cell growth regulation. In vitro experiments demonstrated that downregulation of Ido1 in tumor cells was associated with decreased cell proliferation, increased apoptosis, and changed expression of cell cycle regulatory genes, whereas upregulation of Ido1 in the cells had the opposite effects. Taken together, our findings indicate that Ido1 expression could exert immunological and nonimmunological effects in murine breast tumor cells.
url http://dx.doi.org/10.1155/2012/173029
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AT yunyunsu immunologicalandnonimmunologicaleffectsofindoleamine23dioxygenaseonbreasttumorgrowthandspontaneousmetastasisformation
AT eliesergorelik immunologicalandnonimmunologicaleffectsofindoleamine23dioxygenaseonbreasttumorgrowthandspontaneousmetastasisformation
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