Cancers, Vol. 13, Pages 5338: IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth

Cancers, Vol. 13, Pages 5338: IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth Cancers doi: 10.3390/cancers13215338 Authors: Jiahui Li Xiaolin Wu Lars Schiffmann Thomas MacVicar Chenghui Zhou Zhefang Wang Dai Li Oscar Velazquez Camacho Reiner Heuchel Margarete Odenthal Axel Hillmer Alexander Quaas Yue Zhao Christiane J. Bruns Felix C. Popp 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.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research