Immunological and nonimmunological effects of indoleamine 2,3-dioxygenase on breast tumor growth and spontaneous metastasis formation.
Immunological and nonimmunological effects of indoleamine 2,3-dioxygenase on breast tumor growth and spontaneous metastasis formation.
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吲哚胺2,3-二氧酶对乳腺肿瘤生长和自发转移形成的免疫学和非免疫学作用。
DOI：
10.1155/2012/173029
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发表时间：
2012
影响因子：
--
通讯作者：
Gorelik E
中科院分区：
文献类型：
--
作者：
Levina V;Su Y;Gorelik E
使用两对Ido 1+和Ido 1 −小鼠乳腺癌细胞系分析了色氨酸分解代谢酶吲哚胺2，3-双加氧酶（IDO 1）在肿瘤逃逸和转移形成中的作用。4 T1细胞中Ido 1的表达被shRNA敲低，NT-5细胞中Ido 1的表达被稳定转染上调。在免疫活性小鼠中，Ido 1 −肿瘤的生长和自发转移形成受到抑制。携带Ido 1 −肿瘤的小鼠脾细胞产生的细胞毒性T淋巴细胞水平高于Ido 1+肿瘤。在免疫缺陷小鼠中肿瘤和转移性生长增强，证实了在没有Ido 1表达的情况下增强的免疫应答。然而，在免疫缺陷的SCID/beige小鼠（缺乏T、B和NK细胞）中，Ido 1+肿瘤比Ido 1 −肿瘤生长更快，这表明一些Ido 1控制的非免疫机制可能参与了肿瘤细胞的生长调节。体外实验表明，下调Ido 1在肿瘤细胞中与细胞增殖减少，凋亡增加，细胞周期调控基因的表达改变，而上调Ido 1在细胞中有相反的效果。总之，我们的研究结果表明，Ido 1表达可以发挥免疫和非免疫小鼠乳腺肿瘤细胞的影响。
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.
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影响因子：
3.8
作者：
Ligam, P;Manuelpillai, U;Walker, D
通讯作者：
Walker, D
影响因子：
5
作者：
Huang L;Baban B;Johnson BA 3rd;Mellor AL
通讯作者：
Mellor AL
DOI：
10.1084/jem.189.9.1363
发表时间：
1999-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Munn DH;Shafizadeh E;Attwood JT;Bondarev I;Pashine A;Mellor AL
通讯作者：
Mellor AL
影响因子：
4
作者：
Miwa, N;Hayakawa, S;Saito, S
通讯作者：
Saito, S
影响因子：
4.8
作者：
Hill, M;Pereira, V;Anegon, I
通讯作者：
Anegon, I