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

ABSTRACT: 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 restructu

SUBMITTER: Kang S 

PROVIDER: S-EPMC12353550 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature