Endothelial ganglioside GM3 regulates angiogenesis in solid tumors
Endothelial ganglioside GM3 regulates angiogenesis in solid tumors
复制标题
内皮神经节苷脂 GM3 调节实体瘤中的血管生成
DOI：
10.1016/j.bbrc.2021.06.063
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发表时间：
2021
影响因子：
3.1
通讯作者：
Yamashita Tadashi
中科院分区：
文献类型：
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作者：
Suzuki Mira;Nagane Masaki;Kato Kazuhiro;Yamauchi Akinori;Shimizu Takuto;Yamashita Hiroko;Aihara Naoyuki;Kamiie Junichi;Kawashima Nagako;Naito Shokichi;Yamashita Tadashi
癌细胞生长需要氧气和营养物质，使血管生成成为肿瘤生长的重要组成部分之一。神经节苷脂构成膜脂筏，调节细胞内信号转导，并参与癌细胞的恶性化。虽然内皮细胞以及癌细胞表达大量的神经节苷脂，但内皮神经节苷脂在血管生成中的确切功能仍不清楚。本研究以血管内皮细胞中的神经节苷脂为研究对象，分析其在肿瘤血管生成中的作用。在人乳腺癌中，GM 3合成酶在血管内皮细胞以及免疫细胞中高度表达。在GM 3S-KO小鼠中血管生成增加。在BAEC中，GM 3S的RNA干扰显示通过激活ERK增加细胞侵袭和氧化应激耐受。在乳腺癌模型中，GM 3-KO小鼠显示肿瘤生长和血管生成增加。这些结果表明，内皮神经节苷脂GM 3通过抑制内皮细胞的细胞侵袭和氧化应激耐受来调节肿瘤血管生成。
Cancer cells require oxygen and nutrients for growth, making angiogenesis one of the essential components of tumor growth. Gangliosides, constituting membrane lipid rafts, regulate intracellular signal transduction and are involved in the malignancy of cancer cells. While endothelial cells, as well as cancer cells, express vast amounts of gangliosides, the precise function of endothelial gangliosides in angiogenesis remains unclear. In this study, we focused on gangliosides of vascular endothelial cells and analyzed their functions on tumor angiogenesis. In human breast cancer, GM3 synthase was highly expressed in vascular endothelial cells as well as immune cells. Angiogenesis increased in GM3S–KO mice. In BAEC, RNA interference of GM3S showed increased cellular invasion and oxidative stress tolerance through activation of ERK.In the breast cancer model, GM3-KO mice showed an increase in tumor growth and angiogenesis. These results suggest that the endothelial ganglioside GM3 regulates tumor angiogenesis by suppressing cellular invasion and oxidative stress tolerance in endothelial cells.