Increased tissue and circulating levels of dipeptidyl peptidase-IV enzymatic activity in patients with pancreatic ductal adenocarcinoma
Increased tissue and circulating levels of dipeptidyl peptidase-IV enzymatic activity in patients with pancreatic ductal adenocarcinoma
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DOI：
10.1016/j.pan.2016.06.001
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发表时间：
2016-09-01
期刊：
影响因子：
3.6
通讯作者：
Sedo, Aleksi
中科院分区：
文献类型：
--
作者：
Busek, Petr;Vanickova, Zdislava;Sedo, Aleksi
背景/目标：胰腺导管腺癌（PDAC）经常以葡萄糖稳态受损为先兆。二肽基肽酶-IV (DPP-IV) 和成纤维细胞活化蛋白 α (FAP) 是氨肽酶，可调节参与血糖调节的多种生物活性肽，并且在癌症中经常失调。本研究分析了 PDAC 组织中的血浆水平以及 DPP-IV 和 FAP 的数量和定位。方法：评估了 93 名 PDAC、39 名 2 型糖尿病 (T2DM) 和 29 名对照受试者的血浆以及 48 名 PDAC 患者配对的非肿瘤和肿瘤组织中的 DPP-IV 和 FAP 浓度和酶活性。使用免疫组织化学和催化组织化学测定DPP-IV和FAP的定位。结果：与非肿瘤胰腺相比，PDAC肿瘤组织中DPP-IV的酶活性和浓度较高。 DPP-IV 在癌细胞和激活的（肌）成纤维细胞（包括 DPP-IV(+)FAP(+) 细胞）的纤维化基质中表达。 FAP 在基质细胞和一些癌细胞中表达，并且其表达在肿瘤中增加。与 T2DM 相比，近期发病的 DM 的血浆 DPP-IV 酶活性，特别是 DPP-IV 酶活性与 PDAC 中浓度之间的比率较高。相反，与T2DM和对照相比，PDAC中血浆FAP酶活性较低，并且在肿瘤切除后升高。结论：PDAC组织中DPP-IV样酶活性上调。最近患有糖尿病或糖尿病前期的 PDAC 患者血浆 DPP-IV 酶活性增加。这些变化可能导致经常观察到的 PDAC 与近期出现的血糖调节受损之间的关联。 (C) 2016 年 IAP 和 EPC。由 Elsevier B.V. 出版。保留所有权利。
Background/objectives: Pancreatic ductal adenocarcinoma (PDAC) is frequently heralded by an impairment of glucose homeostasis. Dipeptidyl peptidase-IV (DPP-IV) and fibroblast activation protein alpha (FAP) are aminopeptidases that regulate several bioactive peptides involved in glucoregulation, and are frequently dysregulated in cancer. The present study analyzes blood plasma levels and the quantity and localization of DPP-IV and FAP in PDAC tissues.Methods: DPP-IV and FAP concentration and enzymatic activity were evaluated in the plasma from 93 PDAC, 39 type 2 diabetes mellitus (T2DM) and 29 control subjects, and in matched paired non-tumorous and tumor tissues from 48 PDAC patients. The localization of DPP-IV and FAP was determined using immunohistochemistry and catalytic histochemistry.Results: The enzymatic activity and concentration of DPP-IV was higher in PDAC tumor tissues compared to non-tumorous pancreas. DPP-IV was expressed in cancer cells and in the fibrotic stroma by activated (myo)fibroblasts including DPP-IV(+)FAP(+) cells. FAP was expressed in stromal cells and in some cancer cells and its expression was increased in the tumors. Plasmatic DPP-IV enzymatic activity, and in particular the ratio between DPP-IV enzymatic activity and concentration in PDAC with recent onset DM was higher compared to T2DM. In contrast, the plasmatic FAP enzymatic activity was lower in PDAC compared to T2DM and controls and rose after tumor removal.Conclusions: 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. (C) 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.