Indolcaminc 2, 3-dioxygcnasc 1 is Highly Exprcsscd in Glioma Stcm Cclls.
Indolcaminc 2, 3-dioxygcnasc 1 is Highly Exprcsscd in Glioma Stcm Cclls.
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Indolcaminc 2, 3-dioxygcnasc 1 在胶质瘤细胞中高度表达。
DOI：
10.1016/j.bbrc.2020.01.148
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发表时间：
2020
影响因子：
3.1
通讯作者：
Atsuo Yoshino.
中科院分区：
文献类型：
--
作者：
Yoshinari Ozawa;Shun Yamamuro;Emiko Sano;Juri Tatsuoka;Yuya Hanashima;Sodai Yoshimura;Koichiro Sumi;Hiroyuki Hara;Tomohiro Nakayama;Yutaka Suzuki;Atsuo Yoshino.
最近的研究表明，胶质母细胞瘤（GBM）通过强表达吲哚胺2,3-双加氧酶1 （IDO1）来逃避免疫系统。IDO1是一种参与色氨酸代谢的酶，目前被认为是GBM治疗的新靶点，因为一些报道表明IDO1的表达与GBM恶性肿瘤有关。另一方面，胶质瘤干细胞（glioma stem cells, GSCs）与GBM的恶性程度密切相关是众所周知的。然而，目前还没有报道评价GSCs和IDO1之间的关系。因此，我们检测了IDO1在GSCs中的表达水平，以确定基于GSCs免疫系统的GBM的新治疗靶点。在本研究中，我们使用了人GBM细胞系（U-138MG, U-251MG）和患者来源的GSC模型细胞系（0125-GSC, 0222-GSC）。在无血清培养基中培养U-138MG和U-251MG，建立GSC模型细胞系Rev-U-138MG和Rev-U-251MG；在含血清培养基中培养0125-GSC和0222-GSC，建立GBM分化模型细胞系0125-DGC和0222-DGC。检测干细胞标志物（Nanog、Nestin、Oct4、Sox2）及IDO1蛋白和mRNA的表达水平。与U-138MG和U-251MG相比，Rev-U-138MG和Rev-U-251MG形成球体，干细胞标记物表达量增加。另一方面，0125-DGC和0222-DGC在原有的0125-GSC和0222-GSC形成球的情况下，形成球的过程被破坏，标记物的表达量下降。与U-138MG、U-251MG、0125-GSC和0222-GSC相比，IDO1在Rev-U-138MG、Rev-U-251MG、0125-DGC和0222-DGC中表达较强。这些发现表明，GSCs通过高水平表达IDO1表现出免疫抑制的治疗抗性，可能代表GBM治疗的新靶点。
Recent research has revealed that glioblastoma (GBM) avoids the immune system via strong expression of indoleamine 2,3-dioxygenase 1 (IDO1). IDO1, an enzyme involved in tryptophan metabolism, is now proposed as a new target in GBM treatment, since several reports have demonstrated that IDO1 expression is related to GBM malignancy. On the other hand, it is well known that glioma stem cells (GSCs) are strongly related to the malignancy of GBM. However, there is as yet no report evaluating the relationship between GSCs and IDO1. We therefore examined the expression levels of IDO1 in GSCs in order to identify a new therapeutic target for GBM based on the immune systems of GSCs. In the present study, we employed human GBM cell lines (U-138MG, U-251MG) and patient-derived GSC model cell lines (0125-GSC, 0222-GSC). GSC model cell lines Rev-U-138MG and Rev-U-251MG were established by culturing U-138MG and U-251MG in serum-free media, while differentiated GBM model cell lines 0125-DGC and 0222-DGC were established by culturing 0125-GSC and 0222-GSC in serum-containing media. The expression levels of stem cell markers (Nanog, Nestin, Oct4 and Sox2) and IDO1 protein and mRNA were determined. Rev-U-138MG and Rev-U-251MG formed spheres and their expression levels of stem cell markers were increased as compared to U-138MG and U-251MG. On the other hand, 0125-DGC and 0222-DGC suffered breakdown of sphere formation, despite the original 0125-GSC and 0222-GSC forming spheres, and their expression levels of the markers were decreased. IDO1 expressions were strongly recognized in Rev-U-138MG, Rev-U-251MG, 0125-GSC and 0222-GSC as compared to U-138MG, U-251MG, 0125-DGC and 0222-DGC. These findings demonstrate that GSCs exhibit treatment resistance with immunosuppression via high expression levels of IDO1, and could represent a novel target for GBM treatment.