Bone Tumor Microenvironment Is Associated with Meningioma Enlargement and Inflammatory Transcriptional States

ABSTRACT: Background/Objectives: Meningiomas frequently involve the adjacent skull bone. The bone tumor microenvironment (TME) represents a unique niche in bone-invasive tumors and bone metastases, and can promote tumor progression through tumor–stromal interactions. We hypothesized that the bone TME may contribute to tumor cell transcriptional changes and tumor growth in meningioma. Methods: Human malignant meningioma cell lines, IOMM-Lee and HKBMM, were implanted over the calvarial bone (bone TME) and into the dorsal skin (non-bone TME) of BALB/c-nu/nu mice. Tumors from the IOMM-Lee model underwent bulk RNA sequencing with computational separation of human- and mouse-derived reads, enabling ligand–target interaction analysis of stromal cell-to-tumor cell signaling. Differential gene expression analysis, enrichment analysis, ligand–target interaction analysis, multiplex immunofluorescence, and immunohistochemistry were performed. Results: Tumor volume was significantly greater in the bone TME than in the non-bone TME in both models, whereas the Ki-67 labeling index was significantly reduced. Transcriptomic analysis revealed distinct tumor cell transcriptional states in the bone TME, characterized by upregulation of inflammation-related genes and enrichment of inflammatory signaling pathways, including interferon responses and NF-κB signaling. Ligand–target interaction analysis of stromal cell-to-tumor cell signaling identified stromal IL1B as a candidate regulator of inflammatory transcriptional programs in tumor cells. F4/80-positive macrophages expressed IL-1β, and tumor cells were positive for phospho-IKKα/β and phospho-IκBα in the bone TME. Conclusions: Tumor–stromal interactions potentially involving macrophage-derived IL-1β may be associated with inflammatory transcriptional programs in meningioma cells and with meningioma enlargement in the bone TME. These interactions may be therapeutically relevant in meningioma with bone involvement.

ORGANISM(S): Mus musculus

PROVIDER: GSE336430 | GEO | 2026/09/14

REPOSITORIES: GEO