Results
Title

Targeting interleukin-17 receptor B enhances gemcitabine sensitivity through downregulation of mucins in pancreatic cancer.

Authors

Tsai, Lung-Hung; Hsu, Kai-Wen; Chiang, Cheng-Ming; Yang, Hsiu-Ju; Liu, Yu-Huei; Yang, Shun-Fa; Peng, Pei-Hua; Cheng, Wei-Chung; Wu, Heng-Hsiung

Abstract

Pancreatic cancer is the fourth leading cause of death worldwide due to its poorest prognoses with a 7% 5-year survival rate. Eighty percent of pancreatic cancer patients relapse after chemotherapy and develop early metastasis and drug resistance. Resistance to nucleoside analog gemcitabine frequently used in first-line therapy is an urgent issue in pancreatic cancer treatment. Expression of mucin (MUC) glycoproteins has been shown to enhance chemoresistance via increased cell stemness. Here we show interlukine-17 receptor B (IL-17RB) expression is positively correlated with MUC1 and MUC4 expression in pancreatic cancer cells and tumor tissue. Moreover, IL-17RB transcriptionally up-regulates expression of MUC1 and MUC4 to enhance cancer stem-like properties and resistance to gemcitabine. These results suggest IL-17RB can be a potential target for pancreatic cancer therapy. Indeed, treatment with IL-17RB-neutralizing antibody has a synergistic effect in combination with gemcitabine for killing pancreatic cancer cells. Altogether, these findings provide feasible applications for IL-17RB-targeting therapy in pancreatic cancer treatment.

Subjects

PANCREATIC cancer; CANCER treatment; GLYCOPROTEINS; GENE expression; STEM cells; GEMCITABINE; INTERLEUKIN-17

Publication

Scientific Reports, 2020, Vol 10, Issue 1, p1

ISSN

2045-2322

Publication type

Academic Journal

DOI

10.1038/s41598-020-73659-z