Hyperglycemia-Induced S100A8 and S100A9 Target Akt and NF-kB Signalling in Pancreatic Cancer Cells.

Context In pancreatic cancer (PaCa) S100A8 is highly expressed by stromal cells when SMAD4 is not mutated or by cancer cells when SMAD4 is mutated, suggesting the existence of a link between TGF-b and S100A8 pathways. Moreover S100A8 and its binding partner S100A9 are suggested to be involved in cancer progression and in cancer-associated diabetes mellitus. Objectives To analyze S100A8 and S100A9 expression levels in peripheral blood mononuclear cells of patients with PaCa, chronic pancreatitis (ChrPa) or pancreatobiliary tract tumors (PBT) and to ascertain S100A8/S100A9 interactions with TGF-b1 on PaCa Akt and NF-kB signalling. Methods Fifty-five PaCa, 12 ChrPa and 15 PBT were studied. S100A8 and S100A9 mRNA expression levels were quantified by RT-PCR (Taqman chemistry). Capan-1 (SMAD4 mutated) and MiaPaCa2 (SMAD4 wild type) cell lines were used to analyze S100A8, S100A9 and TGF-b1 effects on Akt (pAkt473) and NF-kB (pIkBa) signalling by western blotting. Results S100A8 and S100A9 expression levels were correlated with each other (r=0.637, P<0.0001), but none of these proteins vary between groups (F=0.65, P NS; F=2.75, P NS) or, in PaCa, between tumor stage (t=1.24, P NS; t=0.56, P NS). S100A8, but mainly S100A9, were directly correlated with fasting plasma glucose (r=0.22, P=0.05; r=0.46, P