The molecular footprint of the serotoninergic system in human glioblastoma cells

Serotonin plays a regulatory role in cancer progression, but its role in glioblastoma growth, the most frequent and aggressive malignant brain tumor, is unclear. The expression and cellular distribution pattern of key components of the serotoninergic system in glioblastoma cells have not been fully characterized. Using transcriptomic analysis of public datasets, we identified subtype-specific expression pattern of serotonin-related genes. The biosynthetic enzymes tryptophan hydroxylase 1 and 2 and the serotonin transporter (SERT/SLC6A4) were enriched in the classical (CL) and proneural (PN) molecular subtypes, whereas monoamine oxidase-A expression was uniformly distributed across all subtypes. Notably, the serotonin receptors HTR1D and HTR7 transcripts were upregulated in ME and CL tumors. Additionally, by using RT-qPCR and immunofluorescence, we observed a differential expression and intracellular distribution pattern of all serotoninergic system elements in human glioblastoma-derived cell lines. Our findings demonstrate the differential expression and cellular localization of the serotoninergic elements in human glioblastomas and suggest their potential participation in their progression.