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...
Main Authors: | , , |
---|---|
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 |
id |
doaj-2bd2379f90d64ad980667f1ce457a504 |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT veralevina immunologicalandnonimmunologicaleffectsofindoleamine23dioxygenaseonbreasttumorgrowthandspontaneousmetastasisformation AT yunyunsu immunologicalandnonimmunologicaleffectsofindoleamine23dioxygenaseonbreasttumorgrowthandspontaneousmetastasisformation AT eliesergorelik immunologicalandnonimmunologicaleffectsofindoleamine23dioxygenaseonbreasttumorgrowthandspontaneousmetastasisformation |
_version_ |
1725772639071371264 |