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.
Int J Oncol. 2010 Feb;36(2):351-8.
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.
脑膜瘤来源于蛛网膜帽细胞，约占颅内肿瘤的 30%。在本研究中，我们检测了 22 例人脑膜瘤中二肽基肽酶（DPP）-IV 活性和/或结构同系物（DASH）的表达，包括经典的 DPP-IV/CD26、成纤维细胞激活蛋白-α（FAPalpha）、DPP8 和 DPP9。通过连续速率荧光法在组织匀浆和原位催化酶组织化学中，在所有 18 例良性脑膜瘤（WHO 分级 I）和 4 例非典型脑膜瘤（WHO 分级 II）中均发现了 DPP-IV 样酶活性，包括所有具有酶活性的 DASH 分子。在非典型脑膜瘤中，这种活性显著升高，并与 Ki67 抗原免疫组化检测到的更高的细胞增殖相关。通过实时 RT-PCR 和免疫组化检测到 DPP-IV/CD26 和 FAPalpha 的表达较低。组织化学显示，它通常发生在富含细胞外基质的纤维束和漩涡的表面。与 DPP-IV/CD26 和 FAPalpha 相比，DPP8 和 DPP9 的表达更高，而且，它也存在于这些结构内部的细胞中。趋化因子基质细胞衍生因子-1α（SDF-1α）的前促增殖受体 CXCR4 的表达存在于所有肿瘤中，表明在非典型 II 级样本中表达值更高。这是首次报道脑膜瘤中二肽基肽酶-IV 和相关分子的表达情况。它表明在所有检查的患者中，DPP8 和 DPP9 比经典的 DPP-IV/CD26 和 FAPalpha 更为常见。此外，该研究表明，这些 WHO 分级 II 的肿瘤中 DPP-IV 样酶活性增加。
