Reduced Pro-coagulant Phenotype of Microparticles in Pancreatic Cancer Patients on Omega-3-Supplemented Gemcitabine Treatment

Pancreatic cancer (PC) is an aggressive cancer associated with advanced disease at diagnosis and lack of effective therapy. Microparticles (MP), biologically active nanoparticles shed from cells, are novel markers of inflammation and might contribute to the growth and spread of PC. The aim of this study is to determine the effects of omega-3 supplementation in PC patients. MP were isolated from blood taken from PC patients undergoing Gemcitabine treatment (n=9, CON), patients undergoing treatment supplemented with omega-3 fatty acids (n=18, Ω-3) and from healthy controls (n=6, HC). MP were stained with AnV (PS-MP) and anti-CD142 to identify those expressing tissue factor (TF), acquired and analysed using flow cytometry. Circulating MP in both groups of PC patients was significantly greater than HC (CON 84±17X105/ml (P<0.03), Ω-3 105±22x105/ml (P<0.05) vs HC 31±10x105/ml), these MP were also significantly more pro-coagulant than HC MP (CON 13795RFU and Ω-3 11232RFU vs HC 7587RFU, P<0.05). MP were significantly greater in number and size at later disease stage in CON (63±19x105/ml stage 3 vs 128±20x105/ml stage 4, P<0.03; HiFSC 156±15 stage 3 vs 533±213 stage 4, P<0.03), and significantly fewer in Ω-3 patients at early disease stage (136±36x105/ml, P<0.03). This effect on size of MP might be explained by in vitro experiments where incubation with rHuTF increased the size of MP released by a PANC1 cells (P<0.05). The percentage of PS-MP was significantly decreased in Ω-3 patients (6.48% vs HC 13.48%, P<0.03). Significant increases in CD142-MP (P<0.05) and the increases in smaller CD142-MP at later disease stage (41±6 stage 3 vs 107±34 stage 4, P<0.03) seen in CON were not seen in Ω-3 patients, but overall Ω-3 patients had significantly greater numbers of smaller CD142-MP (117±24, P<0.03) at earlier disease stage. Our results show that omega-3 supplementation affects the pro-coagulant nature and size of MP in PC patients. Further work is required to assess the effects of omega-3 and the role of MP in PC.