Dipeptidyl peptidase-IV inhibits glioma cell growth independent of its enzymatic activity
| Autor: | Jarmila Stremenova, Petr Busek, Eva Balaziova, Evzen Krepela, Aleksi Sedo, Lucie Sromova, Hynek Strnad, Dalibor Kosek, Marek Hilser, Jana Trylcova |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Dipeptidases Dipeptidyl Peptidase 4 Primary Cell Culture Biology Transfection Biochemistry Dipeptidyl peptidase Extracellular matrix Mice Cell Movement Glioma Cell Adhesion Tumor Cells Cultured medicine Animals Humans Dipeptidyl-Peptidases and Tripeptidyl-Peptidases Cell adhesion Cell Proliferation Immunomagnetic Separation Cell growth Microarray analysis techniques Gene Expression Profiling Cell Cycle Proteolytic enzymes Cell Biology medicine.disease Xenograft Model Antitumor Assays Molecular biology Gene Expression Regulation Neoplastic Cell culture Mutation Signal Transduction |
| Zdroj: | The International Journal of Biochemistry & Cell Biology. 44:738-747 |
| ISSN: | 1357-2725 |
| DOI: | 10.1016/j.biocel.2012.01.011 |
| Popis: | Malignant gliomas exhibit abnormal expression of proteolytic enzymes that may participate in the uncontrolled cell proliferation and aberrant interactions with the brain extracellular matrix. The multifunctional membrane bound serine aminopeptidase dipeptidyl peptidase (DPP)-IV has been linked to the development and progression of several malignancies, possibly both through the enzymatic and nonenzymatic mechanisms. In this report we demonstrate the expression of DPP-IV and homologous proteases fibroblast activation protein, DPP8 and DPP9 in primary cell cultures derived from high-grade gliomas, and show that the DPP-IV-like enzymatic activity is negatively associated with their in vitro growth. More importantly, the DPP-IV positive subpopulation isolated from the primary cell cultures using immunomagnetic separation exhibited slower proliferation. Forced expression of the wild as well as the enzymatically inactive mutant DPP-IV in glioma cell lines resulted in their reduced growth, migration and adhesion in vitro, as well as 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. Gene set enrichment analysis of the differentially expressed genes showed overrepresentation of gene ontology terms 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. |
| Databáze: | OpenAIRE |
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