Giese A, Bjerkvig R, Berens M E, Westphal M
Department of Neurosurgery, University Hospital Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
J Clin Oncol. 2003 Apr 15;21(8):1624-36. doi: 10.1200/JCO.2003.05.063.
Tumors of glial origin consist of a core mass and a penumbra of invasive, single cells, decreasing in numbers towards the periphery and still detectable several centimeters away from the core lesion. Several decades ago, the diffuse nature of malignant gliomas was recognized by neurosurgeons when super-radical resections using hemispherectomies failed to eradicate these tumors. Local invasiveness eventually leads to regrowth of a recurrent tumor predominantly adjacent to the resection cavity, which is not significantly altered by radiation or chemotherapy. This raises the question of whether invasive glioma cells activate cellular programs that render these cells resistant to conventional treatments. Clinical and experimental data demonstrate that glioma invasion is determined by several independent mechanisms that facilitate the spread of these tumors along different anatomic and molecular structures. A common denominator of this cellular behavior may be cell motility. Gene-expression profiling showed upregulation of genes related to motility, and functional studies demonstrated that cell motility contributes to the invasive phenotype of malignant gliomas. There is accumulating evidence that invasive glioma cells show a decreased proliferation rate and a relative resistance to apoptosis, which may contribute to chemotherapy and radiation resistance. Interestingly, interference with cell motility by different strategies results in increased susceptibility to apoptosis, indicating that this dynamic relationship can potentially be exploited as an anti-invasive treatment paradigm. In this review, we discuss mechanisms of glioma invasion, characteristics of the invasive cell, and consequences of this cellular phenotype for surgical resection, oncologic treatments, and future perspectives for anti-invasive strategies.
胶质源性肿瘤由一个核心肿块和一层呈浸润性的单个细胞半暗带组成，这些单个细胞数量朝着周边逐渐减少，在距离核心病灶数厘米处仍可检测到。几十年前，神经外科医生在采用大脑半球切除术进行超根治性切除却未能根除这些肿瘤时，就认识到了恶性胶质瘤的弥漫性本质。局部浸润最终会导致复发性肿瘤主要在切除腔附近重新生长，而放疗或化疗对此并无显著影响。这就引发了一个问题，即浸润性胶质瘤细胞是否激活了使其对传统治疗产生抗性的细胞程序。临床和实验数据表明，胶质瘤的浸润是由多种独立机制决定的，这些机制促进了这些肿瘤沿着不同的解剖和分子结构扩散。这种细胞行为的一个共同特征可能是细胞运动性。基因表达谱分析显示与运动性相关的基因上调，功能研究表明细胞运动性促成了恶性胶质瘤的浸润表型。越来越多的证据表明，浸润性胶质瘤细胞的增殖率降低且对凋亡具有相对抗性，这可能导致化疗和放疗抗性。有趣的是，通过不同策略干扰细胞运动性会导致对凋亡的敏感性增加，这表明这种动态关系有可能被用作一种抗浸润治疗模式。在本综述中，我们讨论了胶质瘤浸润的机制、浸润细胞的特征，以及这种细胞表型对手术切除、肿瘤治疗和抗浸润策略未来前景的影响。
