A collection of R scripts for identifying and characterizing CAFs in gliomas
The abundance and biological contribution of cancer associated fibroblasts (CAFs) in glioblastoma are poorly understood. We applied single-cell RNA sequencing analysis to identify and characterize stromal cells with CAF transcriptomic feature in human glioblastoma tumors and then performed functional enrichment analysis and in vitro assays to investigate their interactions with malignant glioblastoma cells. Results: We found that CAF abundance was low but significantly correlated with tumor grade, poor clinical outcome, and activation of extracellular matrix remodeling, using three large cohorts containing bulk RNA-sequencing data and clinical information. Proteomic analysis of a glioblastoma-derived CAF line and its secretome revealed fibronectin (FN1) as a critical candidate factor mediating CAF functions. This was validated using in vitro cellular models, which demonstrated that CAF conditioned media and recombinant FN1 could facilitate the migration and invasion of glioblastoma cells. In addition, we showed that CAFs were more abundant in the mesenchymal-like state (or subtype) than in other states of glioblastomas, while cell lines resembling the proneural-state responded to the CAF signaling better in terms of the migratory and invasive phenotypes.
Reference: Galbo et al. Functional Contribution and Clinical Implication of Cancer-Associated Fibroblasts in Glioblastoma. PMID:38060213