Malignant gliomas including Glioblastoma (GBM) are characterized by extensive diffuse tumor cell infiltration throughout the brain, which represents a major challenge in clinical disease management. While surgical resection is beneficial for patient outcome, it is well recognized that tumor cells at the invasive front or beyond stay behind and constitute a major source of tumor recurrence. Invasive glioma cells also represent a difficult therapeutic target since they are localized within normal functional brain areas with an intact blood brain barrier (BBB), thereby excluding most systemic drug treatments. Cell movement is mediated via the actin cytoskeleton where corresponding membrane protrusions play essential roles. This review provides an overview of the various paths of glioma cell invasion and underlines the specific aspects of the brain microenvironment. We highlight recent insight into tumor microtubes, neuro-glioma synapses and tumor metabolism which can regulate collective invasion processes. We also focus on the deregulation of actin cytoskeleton-related components in the context of glioma invasion, a deregulation that may be controlled by genomic alterations in tumor cells as well as by various external factors, including extracellular matrix (ECM) components and non-malignant stromal cells. Finally we critically assess the challenges and opportunities for therapeutically targeting glioma cell invasion.

包括胶质母细胞瘤 (GBM) 在内的恶性胶质瘤的特点是在整个大脑中广泛弥漫性肿瘤细胞浸润，这代表了临床疾病管理中的一项重大挑战。虽然手术切除有利于患者的预后，但众所周知，侵袭前沿或远处的肿瘤细胞会留在后面并构成肿瘤复发的主要来源。侵袭性神经胶质瘤细胞也代表了一个困难的治疗目标，因为它们位于具有完整血脑屏障 (BBB) 的正常功能脑区域内，因此排除了大多数全身性药物治疗。细胞运动是通过介导的肌动蛋白细胞骨架，其中相应的膜突起发挥重要作用。本综述概述了胶质瘤细胞侵袭的各种途径，并强调了脑微环境的具体方面。我们强调了最近对可以调节集体侵袭过程的肿瘤微管、神经胶质瘤突触和肿瘤代谢的认识。我们还关注在胶质瘤侵袭背景下肌动蛋白细胞骨架相关成分的失调，这种失调可能受肿瘤细胞基因组改变以及各种外部因素（包括细胞外基质 (ECM) 成分和非恶性）的控制基质细胞。最后，我们批判性地评估了治疗性靶向胶质瘤细胞侵袭的挑战和机遇。