Department of Physiology, Faculty of Medicine and Dentistry, University of Basque Country, Barrio Sarriena s/n, 48940-Leioa, Spain.
BMC Cancer. 2010 May 11;10:193. doi: 10.1186/1471-2407-10-193.
Cell-surface glycoproteins play critical roles in cell-to-cell recognition, signal transduction and regulation, thus being crucial in cell proliferation and cancer etiogenesis and development. DPP IV and NEP are ubiquitous glycopeptidases closely linked to tumor pathogenesis and development, and they are used as markers in some cancers. In the present study, the activity and protein and mRNA expression of these glycoproteins were analysed in a subset of clear-cell (CCRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytomas (RO).
Peptidase activities were measured by conventional enzymatic assays with fluorogen-derived substrates. Gene expression was quantitatively determined by qRT-PCR and membrane-bound protein expression and distribution analysis was performed by specific immunostaining.
The activity of both glycoproteins was sharply decreased in the three histological types of renal tumors. Protein and mRNA expression was strongly downregulated in tumors from distal nephron (ChRCC and RO). Moreover, soluble DPP IV activity positively correlated with the aggressiveness of CCRCCs (higher activities in high grade tumors).
These results support the pivotal role for DPP IV and NEP in the malignant transformation pathways and point to these peptidases as potential diagnostic markers.
细胞表面糖蛋白在细胞间识别、信号转导和调节中发挥着关键作用，因此在细胞增殖和癌症发病机制和发展中至关重要。DPP IV 和 NEP 是普遍存在的糖肽酶，与肿瘤的发生和发展密切相关，它们被用作某些癌症的标志物。在本研究中，分析了一组透明细胞（CCRCC）和嫌色细胞（ChRCC）肾细胞癌以及肾嗜酸细胞瘤（RO）中这些糖蛋白的活性以及蛋白和 mRNA 表达。
用荧光底物的常规酶促测定法测量肽酶活性。通过 qRT-PCR 定量测定基因表达，通过特异性免疫染色分析膜结合蛋白的表达和分布。
三种组织学类型的肾肿瘤中两种糖蛋白的活性均明显降低。来自远曲小管的肿瘤（ChRCC 和 RO）中蛋白和 mRNA 表达强烈下调。此外，可溶性 DPP IV 活性与 CCRCC 的侵袭性呈正相关（高级别肿瘤中活性更高）。
这些结果支持 DPP IV 和 NEP 在恶性转化途径中的关键作用，并指出这些肽酶可能是潜在的诊断标志物。
