CNSC-09. THE NEUROENDOCRINE FACTOR VGF IS NECESSARY FOR THE MAINTENANCE OF THE TUMOR STEM CELL POPULATION IN GLIOBLASTOMA

Abstract A major factor that contributes to the unchecked growth and recurrence of glioblastoma (GBM) tumors is presence a heterogeneous population GBM stem-like cells (GSCs) continuously replenish tumor mass. Targeting strategies against this key cell have rarely considered trophic signals from peritumoral neural cells, which can protect during therapy therefore promote recurrence. Here, we focused on little-known secreted VGF its derived neuropeptides, are largely restricted CNS mediate paracrine communication between cells. We analyzed over 200 tissue specimens cultured demonstrating upregulated in malignant gliomas expressed GSCs different subtypes, although it markedly reduced differentiated More importantly, detected expression astrocytes, even though neuroendocrine has never been described glial normal brain. Co-culture experiments scRNAseq data clinical confirmed tumor-associated suggesting these source GBM. Accordingly, purified exogenous increased proliferation rescued GSC viability when were treated with chemotherapeutic temozolomide. Moreover, decreased inflammatory cytokines activated macrophages, may also contribute local immunosuppression gliomas. Conversely, knockdown was sufficient decrease their viability, self-renewal, stemness-related genes. At molecular level, intracellular calcium Akt/mTOR signaling GSCs, possible G protein coupled receptor-mediated mechanism action. Taken together, our results explore for first time role brain-derived progression, highlighting importance disrupting microenvironment achieve long-term anti-tumor efficacy.