Targeting interleukin-17 receptor B enhances gemcitabine sensitivity through downregulation of mucins in pancreatic cancer.
Targeting interleukin-17 receptor B enhances gemcitabine sensitivity through downregulation of mucins in pancreatic cancer.
复制标题
DOI：
10.1038/s41598-020-73659-z
复制
发表时间：
2020-10-20
影响因子：
4.6
通讯作者：
Wu HH
中科院分区：
文献类型：
--
作者：
Tsai LH;Hsu KW;Chiang CM;Yang HJ;Liu YH;Yang SF;Peng PH;Cheng WC;Wu HH
胰腺癌是世界上第四大死亡原因，因为它的预后最差，5年生存率为7%。80%的胰腺癌患者化疗后复发，并出现早期转移和耐药性。对经常用于一线治疗的核苷类似物吉西他滨的耐药性是胰腺癌治疗中的一个紧迫问题。粘蛋白(MUC)糖蛋白的表达已被证明通过增加细胞干细胞来增强化疗耐药性。在此，我们发现在胰腺癌细胞和肿瘤组织中，白细胞介素17受体B(IL-17RB)的表达与MUC1和MUC4的表达呈正相关。此外，IL-17RB在转录水平上上调MUC1和MUC4的表达，以增强癌症干细胞样特性和对吉西他滨的耐药性。这些结果表明IL-17RB可能成为胰腺癌治疗的潜在靶点。事实上，IL-17RB中和抗体与吉西他滨联合治疗对胰腺癌细胞具有协同作用。总之，这些发现为IL-17Rb靶向治疗胰腺癌提供了可行的应用。
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.
登录
查看更多内容
影响因子：
8
作者：
Huang, C-K;Yang, C-Y;Lee, W-H
通讯作者：
Lee, W-H
影响因子：
2.6
作者：
Baek, Seung-Kuk;Woo, Jeong-Soo;Jung, Kwang-Yoon
通讯作者：
Jung, Kwang-Yoon
影响因子：
3.4
作者：
Saitou, M;Goto, M;Yonezawa, S
通讯作者：
Yonezawa, S
影响因子：
3.1
作者：
Hunninghake GM;Chu JH;Sharma SS;Cho MH;Himes BE;Rogers AJ;Murphy A;Carey VJ;Raby BA
通讯作者：
Raby BA
影响因子：
78.5
作者：
Kufe, Donald W.
通讯作者：
Kufe, Donald W.