Increased tissue and circulating levels of dipeptidyl peptidase-IV enzymatic activity in patients with pancreatic ductal adenocarcinoma
Language English Country Switzerland Media print-electronic
Document type Journal Article
PubMed
27320722
DOI
10.1016/j.pan.2016.06.001
PII: S1424-3903(16)30465-3
Knihovny.cz E-resources
- Keywords
- Diabetes mellitus, Fibroblast activation protein alpha, Peptide hydrolases, Plasma, Stromal cells,
- MeSH
- Adenocarcinoma enzymology MeSH
- Stromal Cells enzymology MeSH
- Diabetes Mellitus, Type 2 enzymology MeSH
- Dipeptidyl Peptidase 4 blood metabolism MeSH
- Adult MeSH
- Carcinoma, Pancreatic Ductal enzymology MeSH
- Endopeptidases MeSH
- Fibrosis MeSH
- Middle Aged MeSH
- Humans MeSH
- Membrane Proteins metabolism MeSH
- Young Adult MeSH
- Myofibroblasts enzymology MeSH
- Pancreatic Neoplasms enzymology MeSH
- Pancreas enzymology MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Serine Endopeptidases metabolism MeSH
- Gelatinases metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Dipeptidyl Peptidase 4 MeSH
- DPP4 protein, human MeSH Browser
- Endopeptidases MeSH
- fibroblast activation protein alpha MeSH Browser
- Membrane Proteins MeSH
- Serine Endopeptidases MeSH
- Gelatinases 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.
References provided by Crossref.org
Does DPP-IV Inhibition Offer New Avenues for Therapeutic Intervention in Malignant Disease?
