Alterations in dipeptidyl peptidase-IV (DPP-IV) enzymatic activity are characteristic of malignant transformation. Through its well-characterized functionality in regulating the activity of bioactive peptides by removal of the N-terminal dipeptide, DPP-IV activity may have profound effects upon metastatic potential and cell growth. Although DPP-IV/CD26 (EC 3.4.14.5) is the canonical representative of the group, a number of other proteins including DPP-7, 8, 9, and seprase/fibroblast activation protein-α (FAP-α) have been shown to have similar enzymatic activity. This study was set up to address the relative representation and enzymatic activity of plasma membrane localized DPP-IV/CD26 and FAP-α in human brain and astrocytic tumours. In parallel, expression of CXCR4, receptor for glioma cell growth stimulator chemokine SDF-1α known to be a DPP-IV substrate, was investigated. This is the first report showing that non-malignant brain tissue contains a DPP-IV-like enzymatic activity attributable mostly to DPP-8/9, while the substantial part of the activity in glioma is due to increased DPP-IV/CD26, localized in both the vascular and parenchymal compartments. DPP-IV enzymatic activity increased dramatically with tumour grade severity. A grade-related increase in CXCR4 receptor paralleled the rise in DPP-IV expression and activity. These data might support a role for DPP-IV regulation of the CXCR4-SDF-1α axis in glioma development.

Background/Aims: The determination of neuron-specific enolase (NSE) is relatively frequently requested in the differential diagnosis of small-cell lung carcinoma and non-small-cell lung carcinoma. The individual results of different immunoassays are often not comparable, which has been confirmed by long-term external quality assessments. In this study, we assessed the possible sources of these differences. Methods: More than 3,000 NSE analyses were performed using seven different immunoassays: DELFIA (PerkinElmer), Elecsys 2010 or Modular Analytics E 170 (Roche), Kryptor (B.R.A.H.M.S.), the enzyme-linked immunosorbent assay DRG and three assays based on immunoradiometric assays (DiaSorin, Immunotech and Schering-CIS). The following parameters were evaluated: precision profile of the individual methods, linearity on dilution and modified recovery, comparability and discrimination of immunoassays, sensitivity, and specificity. Results: There were differences in the correlation of values of certain low-concentration specimens. Some assays correlate well while others do not (up to fivefold difference), especially in the case of controls prepared synthetically. Therefore, the current non-standardized preparation of controls is questionable in our opinion. In the cutoff range, the difference in the results of native samples did not exceed its double value. The variation in values >100 µg/l obtained with different assays is <40%. Conclusion: Our results confirmed expected matrix interferences especially in the range of normal and cutoff NSE concentrations. Another source of discrepancies can be attributed to different antibody affinity to αγ- and γγ-enolase isoenzymes. Finally, improper settings of cutoff values also contribute to the different discrimination of the methods.

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DPP-IV-like enzymatic activity is upregulated in PDAC tissues. PDAC patients with recent onset diabetes or prediabetes have increased plasmatic DPP-IV enzymatic activity. These changes may contribute to the frequently observed association of PDAC and recent onset impairment of glucoregulation.