文章 :

胶质母细胞瘤由实体团块向浸润性生长的转变受侵袭微环境中plexin-B2介导的小胶质细胞定向排列调控

Glioblastoma shift from bulk to infiltrative growth is guided by plexin-B2-mediated microglia alignment in invasive niches 

原文发布日期: 2025-05-29 

英文摘要:

Glioblastoma (GBM) lethality stems from uncontrolled growth and infiltration. Using an immunocompetent murine model, we mapped GBM invasion and tumor-associated microglia and macrophage (TAM) interactions. We show that microglia are mobilized ahead of invasion, transforming morphologically and functionally—first forming glial nets around tumor infiltrates and then organizing into ‘oncostreams’ guiding collective migration. Single-cell RNA sequencing revealed three distinct states for tumor cells and microglia, corresponding to invasive niches versus tumor bulk. The invasive patterns and niche-specific gene signatures of tumor cells and TAMs were validated in human GBMs. We further identified a critical role of plexin-B2 in TAMs for resolving cell collision, aligning GBM cells and restructuring the extracellular matrix. Plexin-B2 ablation in TAMs disrupted invasion tracks, shifting GBM growth from infiltrative to bulk expansion. Understanding niche-specific TAM mobilization and anatomical–functional invasion units opens new strategies to target GBM invasion.

摘要翻译：

胶质母细胞瘤（GBM）的致死性源于其不受控制的生长与浸润特性。通过采用免疫活性小鼠模型，我们系统绘制了GBM侵袭路径及肿瘤相关小胶质细胞/巨噬细胞（TAM）的互作图谱。研究发现，小胶质细胞在肿瘤侵袭前沿被激活，经历形态与功能双重转化：先形成包裹肿瘤浸润区的胶质网，进而组织成引导集体迁移的"癌流结构（oncostreams）"。单细胞RNA测序揭示了肿瘤细胞与小胶质细胞的三种分化状态，分别对应侵袭微环境与瘤体核心区。这种侵袭模式及微环境特异性的肿瘤细胞-TAM基因特征在人类GBM中得到验证。我们进一步发现，TAM中plexin-B2信号通路对解决细胞碰撞、排列GBM细胞及重构细胞外基质具有关键作用。敲除TAM的plexin-B2可破坏侵袭轨迹，使GBM生长模式从浸润性转变为团块扩张。该研究通过解析微环境特异性TAM动员机制及解剖-功能侵袭单元，为靶向GBM侵袭提供了新策略。

原文链接:

https://www.nature.com/articles/s43018-025-00985-4