Glioblastoma (GBM) is the most common and aggressive type of malignant brain tumor in adults. Despite multimodal treatment tumor tend to recur due to a subpopulation of stem-like cells (GSCs) also responsible for therapeutic resistance. GBM grows in a rich neurochemical milieu, but the impact of neurochemicals on gliomagenesis is largely unexplored. Neuropeptides are a group of signaling messengers that have been recognized as potent cellular growth factors for many cell types, including cancer. We hypothesized that neuropeptides could be involved in GSCs intercellular communication and therapeutic resistance.
We characterized for the first time the neuropeptide profile in different GBM molecular subtypes and investigated their role in GSCs therapeutic resistance. Gene expression analysis from pro-neural (PN, better prognosis) and mesenchymal (MES, worse prognosis) GSCs was performed based on the data from a custom RNA array for human neuropeptides.
We found a differentially expressed neuropeptide profile in the different GSCs subtypes. VGF in particular was upregulated in MES compared to the PN subtype. Knockdown of VGF decreased GSCs proliferation and sensitized them to temozolomide therapy.
Neuropeptides could be one of the milieu factors linked to GBM plasticity and provide a new target for adjuvant therapy