Department of Neurology, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
Department of Radiology, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):128-134. doi: 10.1073/pnas.1913511116. Epub 2019 Dec 16.
Mechanical properties of biological tissues and, above all, their solid or fluid behavior influence the spread of malignant tumors. While it is known that solid tumors tend to have higher mechanical rigidity, allowing them to aggressively invade and spread in solid surrounding healthy tissue, it is unknown how softer tumors can grow within a more rigid environment such as the brain. Here, we use in vivo magnetic resonance elastography (MRE) to elucidate the role of anomalous fluidity for the invasive growth of soft brain tumors, showing that aggressive glioblastomas (GBMs) have higher water content while behaving like solids. Conversely, our data show that benign meningiomas (MENs), which contain less water than brain tissue, are characterized by fluid-like behavior. The fact that the 2 tumor entities do not differ in their soft properties suggests that fluidity plays an important role for a tumor's aggressiveness and infiltrative potential. Using tissue-mimicking phantoms, we show that the anomalous fluidity of neurotumors physically enables GBMs to penetrate surrounding tissue, a phenomenon similar to Saffman-Taylor viscous-fingering instabilities, which occur at moving interfaces between fluids of different viscosity. Thus, targeting tissue fluidity of malignant tumors might open horizons for the diagnosis and treatment of cancer.
生物组织的力学特性,尤其是其固态或液态行为,会影响恶性肿瘤的扩散。尽管已知实体瘤往往具有更高的机械硬度,使它们能够在固体周围健康组织中积极侵袭和扩散,但尚不清楚较软的肿瘤如何在更坚硬的环境(如大脑)中生长。在这里,我们使用体内磁共振弹性成像(MRE)来阐明异常流动性对软脑肿瘤侵袭性生长的作用,结果表明侵袭性胶质母细胞瘤(GBM)的含水量较高,但表现出固态的行为。相反,我们的数据表明,含水量比脑组织少的良性脑膜瘤(MEN)的行为具有流体样特征。这两种肿瘤实体在其柔软特性上没有差异这一事实表明,流动性对于肿瘤的侵袭性和浸润性潜能起着重要作用。我们使用组织模拟体证明,神经肿瘤的异常流动性使 GBM 能够穿透周围组织,这种现象类似于萨夫曼-泰勒粘性指进不稳定性,它发生在不同粘度的流体之间的移动界面。因此,针对恶性肿瘤的组织流动性可能为癌症的诊断和治疗开辟新的途径。