Ganglioside GM2, highly expressed in the MIA PaCa-2 pancreatic ductal adenocarcinoma cell line, is correlated with growth, invasion, and advanced stage
Ganglioside GM2, highly expressed in the MIA PaCa-2 pancreatic ductal adenocarcinoma cell line, is correlated with growth, invasion, and advanced stage
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DOI：
10.1038/s41598-019-55867-4
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发表时间：
2019-12-18
影响因子：
4.6
通讯作者：
Ishiwata, Toshiyuki
中科院分区：
文献类型：
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作者：
Sasaki, Norihiko;Hirabayashi, Kenichi;Ishiwata, Toshiyuki
神经节苷脂是一组神经节苷脂，是几种癌症的细胞表面标志物和功能因子。然而，神经节苷脂与胰腺导管腺癌(PDAC)之间的关系还没有很好地阐明。在本研究中，我们研究了神经节苷脂GM2在PDAC中的表达和作用。贴壁条件下GM2+细胞的生长速度明显高于GM2-细胞。当GM2-和GM2+细胞进行三维培养时，几乎所有球中的细胞都表达GM2，包括肿瘤干细胞(CSC)样细胞。糖脂合成抑制剂减少了这些CSC样细胞中GM2的表达和转化生长因子-β1信号，可能是通过抑制GM2和转化生长因子βRII之间的相互作用，抑制侵袭。此外，通过抑制MAPK抑制GM2的表达也减少了转化生长因子-β1信号转导，抑制了侵袭。与GM2-细胞相比，GM2+细胞在裸鼠体内形成更大的皮下肿瘤的几率更高。在PDAC病例中，GM2的表达与年龄较小、肿瘤体积较大、分期较晚和组织学分级较高有关。提示GM2可作为PDAC的一种新的诊断和治疗靶点。
Gangliosides, a group of glycosphingolipids, are known to be cell surface markers and functional factors in several cancers. However, the association between gangliosides and pancreatic ductal adenocarcinoma (PDAC) has not been well elucidated. In this study, we examined the expression and roles of ganglioside GM2 in PDAC. GM2+ cells showed a higher growth rate than GM2- cells in the adherent condition. When GM2- and GM2+ cells were cultured three-dimensionally, almost all cells in the spheres expressed GM2, including cancer stem cell (CSC)-like cells. A glycolipid synthesis inhibitor reduced GM2 expression and TGF-beta 1 signaling in these CSC-like cells, presumably by inhibiting the interaction between GM2 and TGF beta RII and suppressing invasion. Furthermore, suppression of GM2 expression by MAPK inhibition also reduced TGF-beta 1 signaling and suppressed invasion. GM2+ cells formed larger subcutaneous tumors at a high incidence in nude mice than did GM2- cells. In PDAC cases, GM2 expression was significantly associated with younger age, larger tumor size, advanced stage and higher histological grade. These findings suggest that GM2 could be used as a novel diagnostic and therapeutic target for PDAC.