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Expression of dipeptidyl peptidase-IV activity and/or structure homologs in human meningiomas
Jarmila Stremenová1, Vladislav Mares, Vera Lisá
1Joint Laboratory of Cancer Cell Biology of the Institute of Biochemistry and Experimental Oncology of the 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
Abstract:
Meningiomas are tumors derived from arachnoid cap cells that represent approximately 30% of all intracranial tumors. In this study, we investigated 22 human meningiomas for the expression of dipeptidyl peptidase (DPP)-IV activity and/or structure homologs (DASH), including canonical DPP-IV/CD26, fibroblast activation protein-alpha (FAPalpha), DPP8 and DPP9. DPP-IV-like enzymatic activity, including all enzymatically-active DASH molecules, was found in all 18 benign meningiomas WHO grade I and IV atypical meningiomas WHO grade II by continuous rate fluorimetric assay in tissue homogenates and catalytic enzyme histochemistry in situ. In atypical meningiomas, this activity was significantly higher and was associated with higher cell proliferation as detected by Ki67 antigen immunohistochemistry. The expression of DPP-IV/CD26 and FAPalpha demonstrated by real-time RT-PCR and immunohistochemistry was low. As shown histochemically, it occurred most often on the surface of fibrous bundles and whorls rich in extracellular matrix. Compared to DPP-IV/CD26 and FAPalpha, the expression of DPP8 and DPP9 was higher and, in addition, it was present also in the cells inside these structures. Expression of CXCR4, the receptor of pro-proliferative chemokine stromal cell-derived factor-1alpha (SDF-1alpha), DPP-IV substrate, was found in all tumors, suggesting higher values in atypical grade II samples. This is the first report on the expression status of dipeptidyl peptidase-IV and related molecules in meningiomas. It shows that DPP8 and DPP9 prevail over canonical DPP-IV/CD26 and FAPalpha in all examined patients. In addition, the study suggests an increase of DPP-IV-like enzymatic activity in these tumors of WHO grade II.
Insights
This study found increased dipeptidyl peptidase (DPP)-IV enzymatic activity in meningiomas, particularly in atypical tumors. DPP8 and DPP9 expression was higher than DPP-IV/CD26 and FAPalpha, suggesting their role in meningioma progression.
Area of Science:
- Neuro-oncology
- Enzymology
- Molecular Biology
Background:
- Meningiomas are common intracranial tumors originating from arachnoid cap cells.
- Dipeptidyl peptidase (DPP)-IV and its homologs (DASH) are enzymes with roles in various biological processes.
- The expression and activity of DASH molecules in meningiomas are not well understood.
Purpose of the Study:
- To investigate the expression and activity of DPP-IV and related DASH molecules in human meningiomas.
- To correlate enzyme activity with tumor grade and cell proliferation.
- To compare the expression levels of different DASH family members.
Main Methods:
- Analysis of 22 human meningiomas (WHO grade I and II).
- Continuous rate fluorimetric assay for DPP-IV-like enzymatic activity.
- Catalytic enzyme histochemistry for in situ analysis.
- Real-time RT-PCR and immunohistochemistry for DPP-IV/CD26 and FAPalpha expression.
- Ki67 antigen immunohistochemistry for cell proliferation assessment.
Main Results:
- DPP-IV-like enzymatic activity was detected in all meningiomas, with significantly higher levels in atypical (WHO grade II) tumors.
- Higher activity in atypical meningiomas correlated with increased cell proliferation (Ki67).
- DPP8 and DPP9 showed higher expression than DPP-IV/CD26 and FAPalpha across all tumors.
- DPP-IV/CD26 and FAPalpha were mainly found on the surface of extracellular matrix components.
- DPP8 and DPP9 were expressed both on the surface and within tumor cells.
- CXCR4 receptor expression was found in all tumors, with higher levels in atypical samples.
Conclusions:
- DPP8 and DPP9 are the predominant DASH molecules in human meningiomas.
- Increased DPP-IV-like enzymatic activity, driven by DPP8/DPP9, may be associated with meningioma progression and proliferation.
- This is the first study to characterize the expression profile of DPP-IV and related molecules in meningiomas.
