Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma.
Gliomas are primary brain tumors mainly affecting adults. The cellular origin is unknown. The recent identification of tumor-initiating cells in glioma, which share many similarities with normal neural stem cells, has suggested the cell of origin to be a transformed neural stem cell. In previous studies, using the RCAS/tv-a mouse model, platelet-derived growth factor B (PDGF-B)-induced gliomas have been generated from nestin or glial fibrillary acidic protein-expressing cells, markers of neural stem cells. To investigate if committed glial progenitor cells could be the cell of origin for glioma, we generated the Ctv-a mouse where tumor induction would be restricted to myelinating oligodendrocyte progenitor cells (OPCs) expressing 2',3'-cyclic nucleotide 3'-phosphodiesterase. We showed that PDGF-B transfer to OPCs could induce gliomas with an incidence of 33%. The majority of tumors resembled human WHO grade II oligodendroglioma based on close similarities in histopathology and expression of cellular markers. Thus, with the Ctv-a mouse we have showed that the cell of origin for glioma may be a committed glial progenitor cell.
Department of Genetics and Pathology, Uppsala University, Sweden.
N
N
Lindberg
M
M
Kastemar
T
T
Olofsson
A
A
Smits
L
L
Uhrbom
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D000818:Animals; D030161:Avian Proteins / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D005822:Genetic Vectors / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014162:Transfection; D014746:Vimentin / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D030161:Avian Proteins; D010982:Platelet-Derived Growth Factor; D011991:Receptors, Virus; C088745:Tva receptor; D014746:Vimentin; D049452:Green Fluorescent Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha; D051057:Proto-Oncogene Proteins c-akt; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571337:CNP protein, human; C571338:Cnp protein, mouse; D018631:ras Proteins