Rui Ren1,2,3, Jie Yu4, Yan Zhang1, Sheng-Fei Wang1, Xia Guo4, Meng Shen1, Meng-Dan Xu1, Min Jiang1, Qiaoming Zhi3, Kai Chen1, Min Tao1, Meng-Yao Wu1, Dong-Mei Gu4, Wei Li1,5. 1. From the Department of Oncology, the First Affiliated Hospital of Soochow University. 2. Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China. 3. Department of General Surgery. 4. Department of Pathology, the First Affiliated Hospital of Soochow University. 5. Comprehensive Cancer Center, Suzhou Xiangcheng People's Hospital, Suzhou, China.
Abstract
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.
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 cancerpatients, 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.
Authors: Miguel A Ortega; Leonel Pekarek; Oscar Fraile-Martinez; Cielo Garcia-Montero; Miguel A Saez; Angel Asúnsolo; Miguel A Alvarez-Mon; Jorge Monserrat; Lidia Ruiz-Llorente; Natalio García-Honduvilla; Agustin Albillos; Julia Buján; Melchor Alvarez-Mon; Luis G Guijarro Journal: Curr Oncol Date: 2022-03-30 Impact factor: 3.109