Endothelial transdifferentiation of glioma stem cells: a literature review

Endothelial transdifferentiation represents a multifaceted process wherein glioma stem cells (GSCs) gradually adopt endothelial characteristics, marked by the expression of endothelial markers (CD31, CD34) and functional traits, while concurrently relinquishing their stem-like properties. This phenomenon is heterogenous in glioblastoma (GBM) samples, but holds importance in terms of prognosis. Typically occurring within hypoxic environments, particularly in perinecrotic regions, endothelial transdifferentiation is influenced by the secretome of neighboring cells, which orchestrates the activation of various signaling pathways including Notch during endothelial lineage commitment, PI3K/AKT, Wnt/β-catenin and epithelial-mesenchymal transition (EMT) during both commitment and maturation. Initially, GSCs organize into vascular-like channels resembling vasculogenic mimicry and express CD144; however, this signature diminishes as endothelial maturation progresses. GSC-derived endothelial cells (ECs) eventually integrate with normal ECs from the tumor periphery, yielding a mosaic pattern. Endothelial transdifferentiation plays a role in response to standard treatments such as temozolomide chemotherapy and radiotherapy.