Cancers (Oct 2021)

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

  • 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

DOI
https://doi.org/10.3390/cancers13215338
Journal volume & issue
Vol. 13, no. 21
p. 5338

Abstract

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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.

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