PDGF-B-driven gliomagenesis can occur in the absence of the proteoglycan NG2
- Equal contributors
1 National Institute for Cancer Research (IST), IRCCS, Largo Rosanna Benzi 10, 16132 Genoa, Italy
2 Department of Oncology Biology and Genetics (DOBiG), University of Genoa, Largo Rosanna Benzi 10, 16132 Genoa, Italy
3 COMT - Centre for Molecular and Translational Oncology, University of Parma, Via G.P. Usberti 11/A, Parma 43100, Italy
4 Laboratory for Stem Cell Research and Cellular Therapy, Division for Experimental Oncology 2, The National Cancer Institute, Aviano, CRO-IRCCS, Via Pedemontana Occidentale 12, Aviano 33081, Italy
5 Department of Cell Biology, Sciences III, 30 Quai E. Ansermet, 1211 Geneva, 4. Switzerland
BMC Cancer 2010, 10:550 doi:10.1186/1471-2407-10-550Published: 12 October 2010
In the last years, the transmembrane proteoglycan NG2 has gained interest as a therapeutic target for the treatment of diverse tumor types, including gliomas, because increases of its expression correlate with dismal prognosis. NG2 has been shown to function as a co-receptor for PDGF ligands whose aberrant expression is common in gliomas. We have recently generated a glioma model based on the overexpression of PDGF-B in neural progenitors and here we investigated the possible relevance of NG2 during PDGF-driven gliomagenesis.
The survival curves of NG2-KO mice overexpressing PDGF-B were compared to controls by using a Log-rank test. The characteristics of tumors induced in NG2-KO were compared to those of tumors induced in wild type mice by immunostaining for different cell lineage markers and by transplantation assays in adult mice.
We showed that the lack of NG2 does not appreciably affect any of the characterized steps of PDGF-driven brain tumorigenesis, such as oligodendrocyte progenitor cells (OPC) induction, the recruitment of bystander OPCs and the progression to full malignancy, which take place as in wild type animals.
Our analysis, using both NG2-KO mice and a miRNA based silencing approach, clearly demonstrates that NG2 is not required for PDGF-B to efficiently induce and maintain gliomas from neural progenitors. On the basis of the data obtained, we therefore suggest that the role of NG2 as a target molecule for glioma treatment should be carefully reconsidered.