Inflammation Promotes Progression of Pancreatic Cancer Through WNT/β-Catenin Pathway-Dependent Manner

Objective Identify the molecular mechanism of inflammatory stimuli induced pancreatic cancer progression. Methods RNA-seq, microarray assay and bioinformatics analyses were used to identify differentially expressed genes. Immunohistochemical staining was performed to evaluate CD68, CD163, beta-catenin, CD103, CCL3 markers. Quantitative real-time polymerase chain reaction (qRT-PCR), luciferase reporter assay, apoptosis assay, wound healing assay and immunofluorescence were performed to study the relationship of inflammatory stimuli and WNT/beta-catenin pathway. Results Differentially expressed genes of macrophage-conditioned medium-treated pancreatic cancer cells were related with WNT/beta-catenin pathway. Inflammatory stimuli could activate WNT/beta-catenin signaling pathway. In 106 pancreatic cancer patients, nuclear beta-catenin expression of CD68-high group was much higher than CD68-low group (P < 0.05), as same as CD163 (P < 0.05). Inflammatory stimuli downregulated the expression of CCL3 via WNT/beta-catenin pathway and inhibited the chemotaxis of CD103(+) dendritic cells. Six pancreatic cancer prognosis associating genes were upregulated by inflammatory stimuli via WNT/beta-catenin pathway. Transforming growth factor-beta promoted malignant biological behavior of pancreatic cancer cells through WNT/beta-catenin pathway-dependent mechanism. Conclusions Our present study provided a novel mechanism involved in the inflammation-driven cancer progression through tumor immune escape and downstream gene regulation of WNT/beta-catenin pathway-dependent manner.