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

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Nov 13

PMID 34771503

Citations 7

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

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The role of interleukin-17 in inflammation-related cancers.

Zhang X, Li B, Lan T, Chiari C, Ye X, Wang K Front Immunol. 2025; 15:1479505.

PMID: 39906741 PMC: 11790576. DOI: 10.3389/fimmu.2024.1479505.

Prognostic value of FCER1G expression and M2 macrophage infiltration in esophageal squamous cell carcinoma.

Peng W, Zhao Y, Yang N, Fang Y, Wu Y, Feng Z Discov Oncol. 2025; 16(1):113.

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Role and functional mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer (Review).

Liu W, Wang X, Wu W Oncol Rep. 2024; 52(5).

PMID: 39219271 PMC: 11378154. DOI: 10.3892/or.2024.8803.

Mechanistic Insights into the Roles of the IL-17/IL-17R Families in Pancreatic Cancer.

Chen Z, Qiao S, Yang L, Sun M, Li B, Lu A Int J Mol Sci. 2023; 24(17).

PMID: 37686343 PMC: 10487659. DOI: 10.3390/ijms241713539.

Pancreatic stellate cells in pancreatic cancer: as potential targets for future therapy.

Wang Z, He R, Dong S, Zhou W Front Oncol. 2023; 13:1185093.

PMID: 37409257 PMC: 10318188. DOI: 10.3389/fonc.2023.1185093.

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