2026-03-15T11:43:43Z https://nagoya.repo.nii.ac.jp/oai

oai:nagoya.repo.nii.ac.jp:02001444 2023-11-16T01:55:36Z 499:508:509:1631753421512

St8sia1-deficiency in mice alters tumor environments of gliomas, leading to reduced disease severity Zhang, Pu Ohkawa, Yuki Yamamoto, Satoko Momota, Hiroyuki Kato, Akira Kaneko, Kei Natsume, Atsushi Farhana, Yesmin Ohmi, Yuhsuke Okajima, Tetsuya Bhuiyan, Robiul H. Wakabayashi, Toshihiko Furukawa, Keiko Furukawa, Koichi open access Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International glioma ganglioside GD3 synthase knockout microglia tumor environment Ganglioside GD3/GD2 are over-expressed in various neuroectoderm-derived tumors. Previous studies indicated that GD3 is involved in the enhancement of cancer properties such as rapid growth and increased invasiveness. However, little is known about the functions of GD3/GD2 in glioma cells and glioma micro- environments. To clarify the functions of GD3/GD2 in gliomas, we used a mouse glioma model based on the RCAS/Gtv-a system. At first, we compared the gliomas size between wild-type (WT) and GD3 synthase (GD3S) knockout (KO) mice, showing a less malignant histology and slower tumor growth in GD3S-KO mice than in WT mice. Immunohistochemistry of glioma sections from WT and GD3S-KO mice revealed that reactive microglia/macrophages showed different localization patterns between the two genetic types of mice. CD68+ cells were more frequently stained inside glioma tissues of GD3S-KO mice, while they were stained mainly around glioma tissues in WT mice. The number of CD68+ cells markedly increased in tumor tissues of GD3S-KO mice at 2 weeks after injection of transfectant DF-1 cells. Furthermore, CD68+ cells in GD3S(-/-) glioma tissues expressed higher levels of inducible nitric oxide synthase. We observed higher expression levels of pro-inflammatory cytokine genes in primary-cultured glioma cells of WT mice than in GD3S-KO mice. DNA microarray data also revealed differential expression levels of various cytokines and chemokines in glioma tissues between WT and GD3S-KO mice. These results suggest that expression of GD3S allows glioma cells to promote polarization of microglia/macrophages towards M2-like phenotypes by modulating the expression levels of chemokines and cytokines. Nagoya University Graduate School of Medicine, School of Medicine 2021-08 eng departmental bulletin paper VoR https://doi.org/10.18999/nagjms.83.3.535 http://hdl.handle.net/2237/0002001444 https://nagoya.repo.nii.ac.jp/records/2001444 10.18999/nagjms.83.3.535 https://www.med.nagoya-u.ac.jp/medlib/nagoya_j_med_sci/833.html 日本学術振興会 Japan Society for the Promotion of Science 18H02628 スフィンゴ糖脂質と膜分子との複合体による細胞膜と微小環境のシグナル制御機構の解明 日本学術振興会 Japan Society for the Promotion of Science 19K22518 細胞外分泌小胞における糖鎖と膜分子のクラスター形成による微小環境制御の動態解明 0027-7622 2186-3326 Nagoya Journal of Medical Science 83 3 535 549 https://nagoya.repo.nii.ac.jp/record/2001444/files/11_Zhang.pdf application/pdf 2.6 MB 2021-09-16