Arrested neural and advanced mesenchymal differentiation of glioblastoma cells-comparative study with neural progenitors
1 Department of Molecular Pathology and Neuropathology, Chair of Oncology, Medical University of Lodz, Czechoslowacka 8/10, 92-216 Lodz, Poland
2 Department of Oncological Pathology, Chair of Oncology, Medical University of Lodz, Paderewskiego 4, 93-509 Lodz, Poland
3 Department of Neurosurgery, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland
4 Department of Neurosurgery, Polish Mother Memorial Hospital Research Institute Lodz, Rzgowska 281/289, 93-338 Lodz, Poland
5 Department of Neuropathology and Molecular Pathology, Medical University of Gdañsk, Dêbinki 7, 80-211 Gdañsk, Poland
6 Department of Neurology, Temple University School of Medicine, 3401 N Broad St. 558 Parkinson Pavilion, Philadelphia, PA 19140, USA
BMC Cancer 2009, 9:54 doi:10.1186/1471-2407-9-54Published: 14 February 2009
Although features of variable differentiation in glioblastoma cell cultures have been reported, a comparative analysis of differentiation properties of normal neural GFAP positive progenitors, and those shown by glioblastoma cells, has not been performed.
Following methods were used to compare glioblastoma cells and GFAP+NNP (NHA): exposure to neural differentiation medium, exposure to adipogenic and osteogenic medium, western blot analysis, immunocytochemistry, single cell assay, BrdU incorporation assay. To characterize glioblastoma cells EGFR amplification analysis, LOH/MSI analysis, and P53 nucleotide sequence analysis were performed.
In vitro differentiation of cancer cells derived from eight glioblastomas was compared with GFAP-positive normal neural progenitors (GFAP+NNP). Prior to exposure to differentiation medium, both types of cells showed similar multilineage phenotype (CD44+/MAP2+/GFAP+/Vimentin+/Beta III-tubulin+/Fibronectin+) and were positive for SOX-2 and Nestin. In contrast to GFAP+NNP, an efficient differentiation arrest was observed in all cell lines isolated from glioblastomas. Nevertheless, a subpopulation of cells isolated from four glioblastomas differentiated after serum-starvation with varying efficiency into derivatives indistinguishable from the neural derivatives of GFAP+NNP. Moreover, the cells derived from a majority of glioblastomas (7 out of 8), as well as GFAP+NNP, showed features of mesenchymal differentiation when exposed to medium with serum.
Our results showed that stable co-expression of multilineage markers by glioblastoma cells resulted from differentiation arrest. According to our data up to 95% of glioblastoma cells can present in vitro multilineage phenotype. The mesenchymal differentiation of glioblastoma cells is advanced and similar to mesenchymal differentiation of normal neural progenitors GFAP+NNP.