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.
Highlights
Pancreatic cancer is the fourth leading cause of death worldwide, about 85% of pancreatic cancer patients being diagnosed with adenocarcinoma[1,2]
MUC1 and MUC4 both are high-molecular-weight glycoproteins related to poor prognosis in thyroid papillary c arcinoma[14], oral squamous cell c arcinoma[15], and pancreatic ductal adenocarcinoma (PDAC)[16,17]
To evaluate the correlation between Interleukin-17 receptor B (IL-17RB), MUC1 and MUC4, we examined the expression of these genes in a panel of human pancreatic cancer cell lines (Fig. 1B)
Summary
Pancreatic cancer is the fourth leading cause of death worldwide, about 85% of pancreatic cancer patients being diagnosed with adenocarcinoma[1,2]. Treatment with monoclonal antibody against the native form of IL-17RB delays the malignancy of pancreatic cancer cells expressing IL-17RB and significantly extends animal survival. Taken together, these results suggest that IL17B/IL-17RB signaling emerges as an important regulator of pancreatic cancer growth and metastasis, but is a feasible target for pancreatic cancer treatment. IHC results from tissue array showed expression of IL-17RB is positively correlated with MUC1 and MUC4. These findings demonstrate IL-17RB can induce gemcitabine resistance and stemness activity via upregulation of MUC1 and MUC4. Targeting IL-17RB is a feasible therapeutic strategy for pancreatic cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
