MMP9 and S100A9 Expression in Peripheral Blood Mononuclear Cells (PBMC) Are Correlated with Pancreatic Adenocarcinoma (PDAC) and with PDAC-Associated Diabetes Mellitus
Context Tumor-stroma-endocrine interactions favour pancreatic adenocarcinoma (PDAC) growth/ progression and PDAC-associated diabetes mellitus (DM). S100A8/A9 and the matrix methalloproteinases (MMPs) 8 and 9 are overexpressed in PDAC stroma. Objective To verify whether S100A8, S100A9, MMP8 and MMP9 mRNA in peripheral blood mononuclear cells (PBMC) is useful for diagnosing and staging PDAC and/or for detecting PDAC-associated DM. To study the impact of S100A8/A9 and of PDAC-associated growth factors and cytokines on MMPs expression. Methods S100A8, S100A9, MMP8 e MMP9 mRNA were quantified by qRT-PCR in 62 PDAC, 37 chronic pancreatitis, 23 pancreatobiliary tract tumors (PBT) and 30 healthy controls (HC). PBMC (blood donors) were treated with insulin, EGF, TGFb1, S100A8/A9 before MMP8 and MMP9 mRNA analysis. Results: MMP8 and MMP9 were higher in PDAC and in PBT than in HC (Kruskal-Wallis test: P<0.0001). S100A8 (P=0.902) and S100A9 (P=0.303) did not vary. PDAC stage was not correlated with any molecule. At binary logistic regression analysis (PDAC presence or absence as dependent; S100A8, S100A9, MMP8, MMP9, age, gender, CA 19-9, bilirubin, glucose, C-peptide, CRP, and ALT as predictors), only MMP9 (OR=0.69; 95% CI: 0.48-0.99; P=0.047) and CA 19-9 (OR=1.74; 95% CI: 1.31-2.33; P=0.0002) were independently correlated with PDAC. In PDAC, DM was independently correlated only with S100A9 (OR=8.16; 95% CI: 2.31-28.78; P=0.001) and age (OR=1.10; 95% CI: 1.01-1.21; P=0.028). Insulin, EGF and TGFb1 did not affect MMP8 or MMP9 expression. S100A8/A9 significantly induced MMP8 (F=23.68; P=0.002) and MMP9 (F=93.84; P<0.0001) mRNA in PBMC. Conclusion PDAC is associated with an increased MMP9, while PDAC-associated DM is associated with an increased S100A9 expression in PBMC. S100A8/A9 effects on MMPs support the hypothesis of an intriguing relationship between inflammation, diabetes and PDAC.
Copyright (c) 2014 Stefania Moz, Dania Bozzato, Carlo Federico Zambon, Paola Fogar, Michela Pelloso, Anna Caterina Milanetto, Andrea Padoan, Filippo Navaglia, Eliana Greco, Claudio Pasquali, Mario Plebani, Daniela Basso
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