Peripheral Blood Monocytes Predict Clinical Prognosis and Support Tumor Invasiveness Through NF-κB-dependent Upregulation of Snail in Pancreatic Cancer

BACKGROUND:The tumor inflammatory microenvironment plays a vital role in the initiation and progression of pancreatic cancer (PC). Both the lymphocyte-to-monocyte ratio (LMR) and preoperative peripheral blood monocytes are related to the prognosis of PC patients. However, the direct effect of monocytes on PC cells is not fully understood. The current study aimed to assess the effect of monocytes on PC and explore its potential mechanism.METHODS:The cutoff value of peripheral blood monocytes was evaluated by the receiver operating characteristic (ROC) curve. Transwell migration and invasion assays were used to detect the mobility of PC cells. The cytokines derived from monocytes were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Western blotting was utilized to assess the expression of epithelial-mesenchymal transition (EMT) related markers. The expression level of Snail in PC tissue was determined by immunohistochemical (IHC) staining.RESULTS:A high monocyte count was inversely correlated with lymph node status and 5-year overall survival in PC. The PC cells underwent a cellular morphology change and increased cell motility after coculture with THP-1 monocytes. The THP-1 monocytes secreted various proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1α), which activated the nuclear factor-κB (NF-κB) signaling pathway leading to the upregulation of Snail and thereby promoting the EMT of PC cells. The expression level of Snail correlated significantly with the density of peripheral blood monocytes, and their level status was significantly associated with 5-year overall survival.CONCLUSIONS:These findings indicated that elevated monocytes counts were a poor prognostic marker in PC, and monocytes could directly induce the EMT process of PC cells by upregulating Snail expression through the NF-κB signaling pathway.