title: Expression of dipeptidyl peptidase-IV activity and/or structure homologs in human meningiomas.
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.
authors.affiliation: Joint 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.
authors.forename: Jarmila
authors.initials: J
authors.lastname: Stremenová
authors.forename: Vladislav
authors.initials: V
authors.lastname: Mares
authors.forename: Vera
authors.initials: V
authors.lastname: Lisá
authors.forename: Marek
authors.initials: M
authors.lastname: Hilser
authors.forename: Evzen
authors.initials: E
authors.lastname: Krepela
authors.forename: Zdislava
authors.initials: Z
authors.lastname: Vanicková
authors.forename: Martin
authors.initials: M
authors.lastname: Syrucek
authors.forename: Oldrich
authors.initials: O
authors.lastname: Soula
authors.forename: Aleksi
authors.initials: A
authors.lastname: Sedo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D004150:Dipeptidases / Q000235:genetics / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008577:Meningeal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008579:Meningioma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D014408:Biomarkers, Tumor; D004150:Dipeptidases; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D018093:Gelatinases; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C471241:DPP9 protein, human; C487997:DPP8 protein, human