Tamai Sho, Ichinose Toshiya, Tsutsui Taishi, Tanaka Shingo, Garaeva Farida, Sabit Hemragul, Nakada Mitsutoshi
Department of Neurosurgery, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan.
Brain Sci. 2022 Apr 15;12(4):505. doi: 10.3390/brainsci12040505.
A major malignant trait of gliomas is their remarkable infiltration capacity. When glioma develops, the tumor cells have already reached the distant part. Therefore, complete removal of the glioma is impossible. Recently, research on the involvement of the tumor microenvironment in glioma invasion has advanced. Local hypoxia triggers cell migration as an environmental factor. The transcription factor hypoxia-inducible factor (HIF) -1α, produced in tumor cells under hypoxia, promotes the transcription of various invasion related molecules. The extracellular matrix surrounding tumors is degraded by proteases secreted by tumor cells and simultaneously replaced by an extracellular matrix that promotes infiltration. Astrocytes and microglia become tumor-associated astrocytes and glioma-associated macrophages/microglia, respectively, in relation to tumor cells. These cells also promote glioma invasion. Interactions between glioma cells actively promote infiltration of each other. Surgery, chemotherapy, and radiation therapy transform the microenvironment, allowing glioma cells to invade. These findings indicate that the tumor microenvironment may be a target for glioma invasion. On the other hand, because the living body actively promotes tumor infiltration in response to the tumor, it is necessary to reconsider whether the invasion itself is friend or foe to the brain.
胶质瘤的一个主要恶性特征是其显著的浸润能力。当胶质瘤发生时，肿瘤细胞已经扩散到远处。因此，完全切除胶质瘤是不可能的。近年来，关于肿瘤微环境参与胶质瘤侵袭的研究取得了进展。局部缺氧作为一种环境因素会触发细胞迁移。缺氧条件下肿瘤细胞产生的转录因子缺氧诱导因子（HIF）-1α会促进各种侵袭相关分子的转录。肿瘤周围的细胞外基质被肿瘤细胞分泌的蛋白酶降解，同时被促进浸润的细胞外基质所取代。星形胶质细胞和小胶质细胞分别与肿瘤细胞相关，成为肿瘤相关星形胶质细胞和胶质瘤相关巨噬细胞/小胶质细胞。这些细胞也促进胶质瘤的侵袭。胶质瘤细胞之间的相互作用积极促进彼此的浸润。手术、化疗和放疗会改变微环境，使胶质瘤细胞得以侵袭。这些发现表明，肿瘤微环境可能是胶质瘤侵袭的一个靶点。另一方面，由于机体为应对肿瘤会积极促进肿瘤浸润，因此有必要重新考虑侵袭本身对大脑是有益还是有害。
