Abstract
The report analyzes the expression and function of DPP-IV in glioma cells. Variable expression of DPP-IV and homologous proteases fibroblast activation protein, DPP8 and DPP9 was observed in primary cell cultures derived from high-grade gliomas and the overall DPP-IV-like enzymatic activity was negatively associated with their in vitro growth.
The DPP-IV positive subpopulation isolated from the primary cell cultures using immunomagnetic separation exhibited slower proliferation, in addition, transfection of the wild as well as the enzymatically inactive mutant DPP-IV resulted in the reduced growth, migration and adhesion in different glioma cell lines in vitro. It also suppressed glioma growth in an orthotopic xenotransplantation mouse model.
Microarray analysis of glioma cells with forced DPP-IV expression revealed differential expression of several candidate genes not linked to the tumor suppressive effects of DPP-IV in previous studies with enrichment of genes associated with cell proliferation, cell adhesion and migration. In conclusion, our data show that DPP-IV may interfere with several aspects of the malignant phenotype of glioma cells in great part independent of its enzymatic activity.