IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth

In pancreatic ductal adenocarcinoma (PDAC), the tumor stroma constitutes most of the cell mass and contributes to therapy resistance and progression. Here we show a hitherto unknown metabolic cooperation between pancreatic stellate cells (PSCs) and tumor cells through Interleukin 17B/Interleukin 17B...

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Bibliographic Details
Published in:Cancers 2021-10, Vol.13 (21), p.5338
Main Authors: Li, Jiahui, Wu, Xiaolin, Schiffmann, Lars, MacVicar, Thomas, Zhou, Chenghui, Wang, Zhefang, Li, Dai, Camacho, Oscar Velazquez, Heuchel, Reiner, Odenthal, Margarete, Hillmer, Axel, Quaas, Alexander, Zhao, Yue, Bruns, Christiane J., Popp, Felix C.
Format: Article
Language:English
Subjects:
Adenocarcinoma
Autophagy
Cell activation
Cell culture
Chemokines
Cytokines
Feedback
Fibroblasts
Genomes
Glycolysis
Interleukin 6
Kinases
Ligands
Medical prognosis
Metabolism
Metastasis
Mitochondria
Oxidative phosphorylation
Pancreatic cancer
Phosphorylation
Statistical analysis
Stellate cells
Stroma
Tumor cells
Xenografts
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Summary:In pancreatic ductal adenocarcinoma (PDAC), the tumor stroma constitutes most of the cell mass and contributes to therapy resistance and progression. Here we show a hitherto unknown metabolic cooperation between pancreatic stellate cells (PSCs) and tumor cells through Interleukin 17B/Interleukin 17B receptor (IL-17B/IL-17RB) signaling. Tumor-derived IL-17B carrying extracellular vesicles (EVs) activated stromal PSCs and induced the expression of IL-17RB. PSCs increased oxidative phosphorylation while reducing mitochondrial turnover. PSCs activated tumor cells in a feedback loop. Tumor cells subsequently increased oxidative phosphorylation and decreased glycolysis partially via IL-6. In vivo, IL-17RB overexpression in PSCs accelerated tumor growth in a co-injection xenograft mouse model. Our results demonstrate a tumor-to-stroma feedback loop increasing tumor metabolism to accelerate tumor growth under optimal nutritional conditions.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13215338