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, β-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/β-catenin pathway.
Results
Differentially expressed genes of macrophage-conditioned medium-treated pancreatic cancer cells were related with WNT/β-catenin pathway. Inflammatory stimuli could activate WNT/β-catenin signaling pathway. In 106 pancreatic cancer patients, nuclear β-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/β-catenin pathway and inhibited the chemotaxis of CD103+ dendritic cells. Six pancreatic cancer prognosis associating genes were upregulated by inflammatory stimuli via WNT/β-catenin pathway. Transforming growth factor-β promoted malignant biological behavior of pancreatic cancer cells through WNT/β-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/β-catenin pathway-dependent manner.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.