Increased tissue and circulating levels of dipeptidyl peptidase-IV enzymatic activity in patients with pancreatic ductal adenocarcinoma
Jazyk angličtina Země Švýcarsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
27320722
DOI
10.1016/j.pan.2016.06.001
PII: S1424-3903(16)30465-3
Knihovny.cz E-zdroje
- Klíčová slova
- Diabetes mellitus, Fibroblast activation protein alpha, Peptide hydrolases, Plasma, Stromal cells,
- MeSH
- adenokarcinom enzymologie MeSH
- buňky stromatu enzymologie MeSH
- diabetes mellitus 2. typu enzymologie MeSH
- dipeptidylpeptidasa 4 krev metabolismus MeSH
- dospělí MeSH
- duktální karcinom slinivky břišní enzymologie MeSH
- endopeptidasy MeSH
- fibróza MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové proteiny metabolismus MeSH
- mladý dospělý MeSH
- myofibroblasty enzymologie MeSH
- nádory slinivky břišní enzymologie MeSH
- pankreas enzymologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- serinové endopeptidasy metabolismus MeSH
- želatinasy metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dipeptidylpeptidasa 4 MeSH
- DPP4 protein, human MeSH Prohlížeč
- endopeptidasy MeSH
- fibroblast activation protein alpha MeSH Prohlížeč
- membránové proteiny MeSH
- serinové endopeptidasy MeSH
- želatinasy MeSH
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.
Citace poskytuje Crossref.org
Does DPP-IV Inhibition Offer New Avenues for Therapeutic Intervention in Malignant Disease?
