Becker Yvonne, Förster Sarah, Gielen Gerrit H, Loke Ian, Thaysen-Andersen Morten, Laurini Christine, Wehrand Kristin, Pietsch Torsten, Diestel Simone
Institute of Nutrition and Food Sciences, Department of Human Metabolomics, University of Bonn, Bonn 53115, Germany.
Institute of Neuropathology, University of Bonn Medical Center, Bonn 53127, Germany.
Oncotarget. 2019 Jul 9;10(43):4449-4465. doi: 10.18632/oncotarget.27056.
Glioblastoma multiforme is an aggressive cancer type with poor patient outcomes. Interestingly, we reported previously a novel association between the little studied paucimannosidic -linked glycoepitope and glioblastoma. Paucimannose has only recently been detected in vertebrates where it exhibits a very restricted tumor-specific expression. Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells. Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion. Finally, we identified AHNAK which is discussed as a tumor suppressor as the first paucimannose-carrying protein in glioblastoma and show the involvement of AHNAK in the observed paucimannose-dependent effects. This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further support may have far reaching benefits for patients suffering from this often fatal disease.
多形性胶质母细胞瘤是一种侵袭性癌症类型，患者预后较差。有趣的是，我们之前报道了一种鲜为人知的寡甘露糖连接糖表位与胶质母细胞瘤之间的新关联。寡甘露糖最近才在脊椎动物中被检测到，在脊椎动物中它表现出非常有限的肿瘤特异性表达。在此，我们首次证明在人类IV级胶质母细胞瘤以及U-87MG和U-138MG胶质母细胞瘤细胞中存在非常高的蛋白质寡甘露糖化。此外，我们揭示了寡甘露糖表位参与包括细胞增殖、迁移、侵袭和黏附在内的致瘤过程。最后，我们鉴定出被认为是肿瘤抑制因子的AHNAK作为胶质母细胞瘤中首个携带寡甘露糖的蛋白质，并表明AHNAK参与了观察到的寡甘露糖依赖性效应。这项研究首次提供了寡甘露糖化在胶质母细胞瘤中具有保护作用的证据，这种关系若得到进一步支持，可能会给患有这种常致命疾病的患者带来深远益处。
