Karmelić Ivana, Jurilj Sajko Mia, Sajko Tomislav, Rotim Krešimir, Fabris Dragana
Department of Medical Chemistry, Biochemistry and Clinical Chemistry, School of Medicine, University of Zagreb, Zagreb, Croatia.
Department of Neurosurgery, University Hospital Center "Sestre milosrdnice", Zagreb, Croatia.
Front Cell Dev Biol. 2024 Dec 11;12:1466141. doi: 10.3389/fcell.2024.1466141. eCollection 2024.
Gliomas are highly aggressive primary brain tumors, with glioblastoma multiforme being the most severe and the most common one. Aberrations in sphingolipid metabolism are a hallmark of glioma cells. The sphingolipid rheostat represents the balance between the pro-apoptotic ceramide and pro-survival sphingosine-1-phosphate (S1P), and in gliomas it is shifted toward cell survival and proliferation, promoting gliomas' aggressiveness, cellular migration, metastasis, and invasiveness. The sphingolipid rheostat can be altered by targeting enzymes that directly or indirectly affect the ratio of ceramide to S1P, leading to increased ceramide or decreased S1P levels. Targeting the sphingolipid rheostat offers a potential therapeutic pathway for glioma treatment which can be considered through reducing S1P levels or modulating S1P receptors to reduce cell proliferation, as well as through increasing ceramide levels to induce apoptosis in glioma cells. Although the practical translation into clinical therapy is still missing, sphingolipid rheostat targeting in gliomas has been of great research interest in recent years with several interesting achievements in the glioma therapy approach, offering hope for patients suffering from these vicious malignancies.
神经胶质瘤是极具侵袭性的原发性脑肿瘤，多形性胶质母细胞瘤是其中最严重且最常见的一种。鞘脂代谢异常是神经胶质瘤细胞的一个标志。鞘脂稳态代表促凋亡神经酰胺和促生存鞘氨醇-1-磷酸（S1P）之间的平衡，在神经胶质瘤中，这种平衡向细胞存活和增殖方向偏移，促进了神经胶质瘤的侵袭性、细胞迁移、转移和浸润。鞘脂稳态可通过靶向直接或间接影响神经酰胺与S1P比例的酶来改变，从而导致神经酰胺水平升高或S1P水平降低。靶向鞘脂稳态为神经胶质瘤治疗提供了一条潜在的治疗途径，可通过降低S1P水平或调节S1P受体来减少细胞增殖，以及通过提高神经酰胺水平来诱导神经胶质瘤细胞凋亡。尽管目前仍缺乏向临床治疗的实际转化，但近年来，针对神经胶质瘤的鞘脂稳态靶向研究引起了极大的兴趣，并在神经胶质瘤治疗方法上取得了一些有趣的成果，为患有这些恶性肿瘤的患者带来了希望。
