Hypoxia modulation of peroxisome proliferator-activated receptors (PPARs) in human glioblastoma stem cells. Implications for therapy.
Gliobastoma (GB), the most common adult brain tumor, infiltrates normal brain area rendering impossible the complete surgical resection, resulting in a poor median survival (14-15 months), despite the aggressive multimodality treatments post-surgery, such as radiation and chemo-therapy. GB is characterized by hypoxic and necrotic regions due to a poorly organized tumor vascularization, leading to inadequate blood supply and consequently to hypoxic and necrotic areas. We have previously shown that, under hypoxia GB primary cells increased the expression of stemness markers as well as the expression of the nuclear receptor peroxisome proliferator-activated receptor α (PPARα) and also the crucial role played by PPARs in mouse neural stem cells maintenance and differentiation. Due to the importance of lipid signaling in cell proliferation and differentiation, in this work, we analyzed the expression of PPARs in GB neurospheres both in normoxic and hypoxic conditions. The results obtained suggest a differential regulation of the three PPARs by hypoxia, thus indicating a possible therapeutic strategy to counteract GB recurrencies.
Department of Health Sciences, University of L'Aquila, L'Aquila, Italy.
Renato
R
Galzio
Loredana
L
Cristiano
Alessia
A
Fidoamore
Maria Grazia
MG
Cifone
Elisabetta
E
Benedetti
Benedetta
B
Cinque
Paola
P
Menghini
Sohelia
S
Raysi Dehcordi
Rodolfo
R
Ippoliti
Antonio
A
Giordano
Annamaria
A
Cimini
D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008856:Microscopy, Fluorescence; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000494:pharmacology*; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D048068:PPAR-beta / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
D015415:Biomarkers; D047493:PPAR alpha; D047495:PPAR gamma; D048068:PPAR-beta; D002784:Cholesterol; D010100:Oxygen