Spatial Cross-talk Modeling of the Tumor Microenvironment Identifies CCR5-Mediated Glia-to-Glia Signaling as a Key Regulator of Brain Metastatic Progression.

ABSTRACT: Glial cells play a critical role in shaping the tumor microenvironment in brain metastases (BM), facilitating disease progression through complex tumor-glial cell and distinct glia-to-glia signaling pathways. To investigate these interactions, we performed RNA sequencing of astrocytes, microglia, and oligodendrocytes at various stages of brain metastatic progression, combined with spatial transcriptomics and cell-cell cross-talk analysis. Glial cells not only converged on tumor-promoting pathways such as Ras and Gap junction signaling in tumor cells but also engaged in distinct autocrine and paracrine signaling critical for interglial communication. Unique ligand-receptor pairs, including OSM-OSMR, CCL4-CCR5, CXCL16-CXCR6, IL1A/B-IL1R, and TNF-TNFR, functioned as key drivers of interglial

SUBMITTER: Ahn JY 

PROVIDER: S-EPMC12656220 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature