Neurosurgery Department, The Third Hospital of Jilin University, Changchun, China.
J Cell Mol Med. 2020 Aug;24(16):9055-9066. doi: 10.1111/jcmm.15542. Epub 2020 Jun 28.
Glioma is one of the most lethal tumours and common malignant in the central nervous system (CNS), which exhibits diffuse invasion and aggressive growth. Several studies have reported the association of FDPS to tumour development and progression. However, the role of FDPS in progression of glioma and macrophage recruitment is not well-elucidated. In the current study, a remarkable enhancement in FDPS level was observed in glioma tissues and associated with poor prognosis, contributed to tumour growth. FDPS was correlated with macrophage infiltration in glioma and pharmacological deletion of macrophages largely abrogated the oncogenic functions of FDPS in glioma. Mechanistically, FDPS activated Wnt/β-catenin signalling pathway and ultimately facilitates macrophage infiltration by inducing CCL20 expression. In conclusion, overexpressed FDPS exhibits an immunomodulatory role in glioma. Therefore, targeting FDPS may be an effective therapeutic strategy for glioma.
神经胶质瘤是中枢神经系统（CNS）中最致命和最常见的恶性肿瘤之一，具有弥漫性浸润和侵袭性生长的特点。有几项研究报道了 FDPS 与肿瘤发生和进展的相关性。然而，FDPS 在神经胶质瘤进展和巨噬细胞募集中的作用尚不清楚。在本研究中，我们观察到 FDPS 水平在神经胶质瘤组织中显著升高，并与预后不良相关，促进了肿瘤的生长。FDPS 与神经胶质瘤中的巨噬细胞浸润相关，药理学去除巨噬细胞在很大程度上消除了 FDPS 在神经胶质瘤中的致癌功能。在机制上，FDPS 通过诱导 CCL20 的表达激活 Wnt/β-catenin 信号通路，进而促进巨噬细胞浸润。总之，过表达的 FDPS 在神经胶质瘤中表现出免疫调节作用。因此，靶向 FDPS 可能是神经胶质瘤的一种有效治疗策略。
