MSLN induced EMT, cancer stem cell traits and chemotherapy resistance of pancreatic cancer cells
Jili Hu,
Jia Wang,
Xu Guo,
Qing Fan,
Xinming Li,
Kai Li,
Zhuoyin Wang,
Shuntao Liang,
Buhe Amin,
Nengwei Zhang,
Chaowen Chen,
Bin Zhu
Affiliations
Jili Hu
Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Henan, 450052, China; The First Affiliated Hospital of Zhengzhou University & Institute of Reproductive Health, Henan Academy of Innovations In Medical Science & NHC Key Laboratory of Birth Defects Prevention, China
Jia Wang
Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China; Department of General Surgery, Third Hospital, Peking University, Beijing, 100871, China
Xu Guo
Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
Qing Fan
Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
Xinming Li
Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
Kai Li
Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
Zhuoyin Wang
Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
Shuntao Liang
Center for Biomedical Innovation, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
Buhe Amin
Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
Nengwei Zhang
Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
Chaowen Chen
Department of General Surgery, Third Hospital, Peking University, Beijing, 100871, China; Corresponding author.
Bin Zhu
Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China; Department of General Surgery, Beijing Shijitan Hospital, Peking University Ninth School of Clinical Medicine, Beijing, China; Corresponding author. Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
Chemoresistance is one of the main reasons for poor prognosis of pancreatic cancer. The effects of mesothelin (MSLN) on chemoresistance in pancreatic cancer are still unclear. We aim to investigate potential roles of MSLN in chemoresistance and its relationship with proliferation, epithelial-mesenchymal transition (EMT) and cancer stemness of pancreatic cancer cells. Human pancreatic cancer cell lines ASPC-1 and Mia PaCa-2 with high and low expression of MSLN, respectively, were selected. The ASPC-1 with MSLN knockout (KO) and Mia PaCa-2 of MSLN overexpression (OE) were generated. The effects of MSLN on cell phenotypes, expression of EMT-related markers, clone formation, tumor sphere formation, and pathologic role of MSLN in tumorigenesis were detected. Sensitivity of tumor cells to gemcitabine was evaluated. The results showed that adhesion, proliferation, migration and invasion were decreased significantly in ASPC-1 with MSLN KO, whereas increased significantly in Mia PaCa-2 with MSLN OE. The size and the number of clones and tumor spheres were decreased in ASPC-1 with MSLN KO, and increased in Mia PaCa-2 with MSLN OE. In xenograft model, tumor volume was decreased (tumor grew slower) in MSLN KO group compared to control group, while increased in MSLN OE group. Mia PaCa-2 with MSLN OE had a higher IC50 of gemcitabine, while ASPC-1 with MSLN KO had a lower IC50. We concluded that MSLN could induce chemoresistance by enhancing migration, invasion, EMT and cancer stem cell traits of pancreatic cancer cells. Targeting MSLN could represent a promising therapeutic strategy for reversing EMT and chemoresistance in pancreatic cancer cells.