In:
Pancreas, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. 8 ( 2019-9), p. 1003-1014
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1536-4828
,
0885-3177
DOI:
10.1097/MPA.0000000000001386
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2019
detail.hit.zdb_id:
2053902-2
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