Energetic Metabolism in Glioblastoma Stem Cells: Effects of PPARalpha Antagonists

Glioblastoma multiforme (GBM, grade IV astrocytoma) is the most malignant and aggressive of brain tumors with poor prognosis and a median survival of patients of approximately 15 months. Over the past decade there has been an increasing interest in the role of cancer stem cells in the tumorigenesis process, because they are responsible of tumor drug resistance and relapse. It is known that glioblastoma stem cells (GSCs) are a heterogeneous population that resides in the intratumoral perivascular and necrotic/hypoxic niches and that hypoxia exerted a crucial function, maintaining stemness and governing their fate. Particularly, hypoxia inducible factors (HIFs) regulate many aspects of tumor malignant progression such as proliferation, angiogenesis, metastasis and metabolism, whose mechanisms, in GSCs, today are poorly understood. In the brain Peroxisome proliferator activated Receptors (PPARs), ligand-activated transcription factors, belonging to the nuclear hormone receptor superfamily, play a specific role in the energetic metabolism. Three isotypes have been described, the α, β and γ, that have a tissue specific distribution and pleiotropic functions as they are involved in many ways in cell proliferation, differentiation, glucose and lipid metabolism.