NG2-expressing glial precursor cells are a new potential oligodendroglioma cell initiating population in N-ethyl-N-nitrosourea-induced gliomagenesis.
Gliomas are the most common primary brain tumor affecting human adults and remain a therapeutic challenge because cells of origin are still unknown. Here, we investigated the cellular origin of low-grade gliomas in a rat model based on transplacental exposure to N-ethyl-N-nitrosourea (ENU). Longitudinal magnetic resonance imaging coupled to immunohistological and immunocytochemical analyses were used to further characterize low-grade rat gliomas at different stages of evolution. We showed that early low-grade gliomas have characteristics of oligodendroglioma-like tumors and exclusively contain NG2-expressing slow dividing precursor cells, which express early markers of oligodendroglial lineage. These tumor-derived precursors failed to fully differentiate into oligodendrocytes and exhibited multipotential abilities in vitro. Moreover, a few glioma NG2+ cells are resistant to radiotherapy and may be responsible for tumor recurrence, frequently observed in humans. Overall, these findings suggest that transformed multipotent NG2 glial precursor cell may be a potential cell of origin in the genesis of rat ENU-induced oligodendroglioma-like tumors. This work may open up new perspectives for understanding biology of human gliomas.
Briançon-Marjollet
Anne
A
INSERM U873, 38054 Grenoble, France.
Balenci
Laurent
L
Fernandez
Manuel
M
Estève
François
F
Honnorat
Jérôme
J
Farion
Régine
R
Beaumont
Marine
M
Barbier
Emmanuel
E
Rémy
Chantal
C
Baudier
Jacques
J
D000818:Animals; D000941:Antigens / Q000032:analysis*; D001932:Brain Neoplasms / Q000139:chemically induced* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005038:Ethylnitrosourea / Q000633:toxicity*; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology*; D009837:Oligodendroglioma / Q000139:chemically induced* / Q000473:pathology; D011509:Proteoglycans / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020703:ras GTPase-Activating Proteins / Q000032:analysis; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D005038:Ethylnitrosourea; D011509:Proteoglycans; D020703:ras GTPase-Activating Proteins; D000099216:Chondroitin Sulfate Proteoglycan 4; C101203:IQ motif containing GTPase activating protein 1