PDGF-B induces a homogeneous class of oligodendrogliomas from embryonic neural progenitors.
We describe the generation of mouse gliomas following the overexpression of PDGF-B in embryonic neural progenitors. Our histopathological, immunohistochemical and genome-wide expression analyses revealed a surprising uniformity among PDGF-B induced tumors, despite they were generated by transducing a highly heterogeneous population of progenitor cells known for their ability to produce all the cell types of the central nervous system. Comparison of our microarray data with published gene expression data sets for many different murine neural cell types revealed a closest correlation between our tumor cells and oligodendrocyte progenitor cells, confirming definitively that PDGF-B-induced gliomas are pure oligodendrogliomas. Importantly, we show that this uniformity is likely due to the ability of PDGF-B overexpression to respecify competent embryonic neural precursors toward the oligodendroglial lineage, providing evidence that the transforming activity of PDGF-B is influenced by the developmental potential of the targeted cells. Interestingly, we found that PDGF-B-induced tumors harbor different proliferating cell populations. However only PDGF-B-overexpressing cells are tumorigenic, indicating that paracrine signaling from the tumor is unable to transform bystander cells.
Appolloni
Irene
I
Department of Genic Transfer, National Institute for Cancer Research (IST), IRCCS, Largo Rosanna Benzi 10, 16132 Genoa, Italy.
Calzolari
Filippo
F
Tutucci
Evelina
E
Caviglia
Sara
S
Terrile
Marta
M
Corte
Giorgio
G
Malatesta
Paolo
P
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009837:Oligodendroglioma / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism / Q000502:physiology*
D020574:Proto-Oncogene Proteins c-sis