文章：

轻脑膜转移的途径

The path to leptomeningeal metastasis

原文发布日期：2024-06-13

DOI: 10.1038/s41568-024-00700-y

类型: Review Article

开放获取: 否

英文摘要：

The leptomeninges, the cerebrospinal-fluid-filled tissues surrounding the central nervous system, play host to various pathologies including infection, neuroinflammation and malignancy. Spread of systemic cancer into this space, termed leptomeningeal metastasis, occurs in 5–10% of patients with solid tumours and portends a bleak clinical prognosis. Previous, predominantly descriptive, clinical studies have provided few insights. Recent development of preclinical leptomeningeal metastasis models, alongside genomic, transcriptomic and proteomic sequencing efforts, has provided groundwork for mechanistic understanding and identification of long-needed therapeutic targets. Although previously understood as an anatomically isolated compartment, the leptomeninges are increasingly appreciated as a major conduit of communication between the systemic circulation and the central nervous system. Despite the unique nature of the leptomeningeal microenvironment, the general principles of metastasis hold true: cells metastasizing to the leptomeninges must gain access to the new environment, survive within the space and evade the immune system. The study of leptomeningeal metastasis has the potential to uncover novel site-specific metastatic principles and illuminate the physiology of the leptomeningeal space. In this Review, we provide a biology-focused overview of how metastatic cells reach the leptomeninges, thrive in this nutritionally sparse environment and evade the detection of the omnipresent immune system.

摘要翻译： 

软脑膜是充满脑脊液的组织，包裹着中枢神经系统，是多种病理改变的场所，包括感染、神经炎症和恶性肿瘤。全身性癌症扩散至该区域被称为软脑膜转移，发生在5%-10%的实体瘤患者中，预示着不良的临床预后。以往以描述性为主的临床研究未能提供深入见解。近期临床前软脑膜转移模型的发展，结合基因组学、转录组学和蛋白质组学测序研究，为机制理解和寻找长期缺失的治疗靶点奠定了基础。虽然过去将软脑膜视为解剖学上的独立腔室，但现在越来越多研究认识到它是体循环与中枢神经系统间的重要交流通道。尽管软脑膜微环境具有独特性，但转移的基本原理仍然适用：转移至软脑膜的癌细胞必须适应新环境，在该空间中存活并逃避免疫系统。对软脑膜转移的研究有望揭示新的位点特异性转移机制，并阐明软脑膜间隙的生理特性。本综述以生物学视角重点阐述转移细胞如何抵达软脑膜、如何在这个营养匮乏的环境中存活，以及如何规避无处不在的免疫系统的监测。

原文链接：

The path to leptomeningeal metastasis