The Joint Laboratory of Cancer Cell Biology of the Institute of Physiology of the Academy of Sciences of the Czech Republic, v.v.i. and the 1st Medical Faculty, Charles University in Prague, Czech Republic.
Histol Histopathol. 2012 Jul;27(7):931-40. doi: 10.14670/HH-27.931.
γ-Glutamyltranspeptidase (GGT, syn. γ-Glutamyltransferase) and dipeptidylpeptidase-IV (DPP-IV) activity participates in metabolic and growth control of normal and tumor cells by processing biologically active peptides. Here, we report on up-regulation of these enzymes in human brain gliomas determined by catalytic enzyme histochemistry and immunocytochemistry. Higher activity of GGT was found in 50%, 68% and 81% of WHO grade II, III and IV tumors, respectively. The process started at/near the microvasculature, from where it spread to the parenchyma. On average, the enzyme activity in grade II, III and IV gliomas exceeded controls 2.0, 3.0 and 3.5-fold, respectively. Up-regulation of DPP-IV-like activity also started at the microvasculature, but mainly in pericytes and mononuclear-like cells around the vessels and dispersed in the parenchyma. Marked elevation of this enzyme activity, comprising also tumor parenchyma, occurred only in grade IV glioblastomas (65% patients; 3.6 times above controls) which can, therefore, help in their differentiation from grade III gliomas. The increase of total DPP-IV-like activity also included its two enzymatic homologs, the canonical DPP-IV/CD26 and FAP-1α. The increase in GGT is supposed to be a tumor grade dependent response of microvasculature and tumor astrocytes to stress induced by tissue hypoxia and/or the metabolic aberrancies. The increase in DPP-IV-like activity in high-grade tumors can be attributed to inflammatory/scavenging processes performed by the mononuclear-like cells and, in glioblastomas, also to regressive changes in the structure and function of the microvasculature and tumor parenchyma, including astrocyte stress response. The inverse relationship between DPP-IV-like activity and Ki67 in most glioblastomas and shorter survival time of patients with low activity of this enzyme also suggest its anti-oncogenic effects.
γ-谷氨酰转肽酶（GGT，又名γ-谷氨酰转移酶）和二肽基肽酶-IV（DPP-IV）通过加工生物活性肽参与正常和肿瘤细胞的代谢和生长控制。在这里，我们通过催化酶组织化学和免疫细胞化学报告了这些酶在人脑胶质瘤中的上调。发现 GGT 活性在 WHO 分级 II、III 和 IV 肿瘤中分别升高了 50%、68%和 81%。该过程从微血管开始/附近开始，并向实质扩散。平均而言，II 级、III 级和 IV 级胶质瘤中的酶活性分别比对照高出 2.0、3.0 和 3.5 倍。DPP-IV 样活性的上调也从微血管开始，但主要在血管周围的周细胞和单核样细胞中，并散布在实质中。只有 IV 级胶质母细胞瘤（65%的患者；比对照高出 3.6 倍）显著升高了这种酶活性，包括肿瘤实质，因此有助于将其与 III 级胶质瘤区分开来。总 DPP-IV 样活性的增加还包括其两种酶同系物，即经典的 DPP-IV/CD26 和 FAP-1α。GGT 的增加被认为是微血管和肿瘤星形胶质细胞对组织缺氧和/或代谢异常引起的应激的肿瘤分级依赖性反应。高级别肿瘤中 DPP-IV 样活性的增加可归因于单核样细胞进行的炎症/清除过程，在胶质母细胞瘤中，还归因于微血管和肿瘤实质的结构和功能的退行性变化，包括星形胶质细胞应激反应。大多数胶质母细胞瘤中 DPP-IV 样活性与 Ki67 呈负相关，以及该酶活性低的患者存活时间较短，这也表明其具有抗肿瘤作用。
