PSC-derived Galectin-1 inducing epithelial-mesenchymal transition of pancreatic ductal adenocarcinoma cells by activating the NF-κB pathway
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Dong Tang1,*, Jingqiu Zhang1,*, Zhongxu Yuan2,*, Hongpeng Zhang1, Yang Chong1, Yuqin Huang1, Jie Wang1, Qingquan Xiong1, Sen Wang3, Qi Wu4, Ying Tian4, Yongdie Lu4, Xiao Ge4, Wenjing Shen4 and Daorong Wang1
1Department of General Surgery, Institute of General Surgery, Northern Jiangsu Province Hospital, Clinical Medical College, Yangzhou University, Yangzhou, P.R. China
2Department of General Surgery, Anhui No. 2 Provincial People’s Hospital, Hefei, Anhui Province, P.R. China
3Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China
4Department of Clinical Medicine, Medical College of Yangzhou University, Yangzhou, P.R. China
*These authors have contributed equally to this work
Dong Tang, email: [email protected]
Daorong Wang, email: [email protected]
Keywords: Galectin-1, invasion, metastasis, pancreatic ductal adenocarcinoma (PDAC), epithelial-mesenchymal transition (EMT)
Received: July 22, 2017 Accepted: August 29, 2017 Published: September 23, 2017
Galectin-1 has previously been shown to be strongly expressed in activated pancreatic stellate cells (PSCs) and promote the development and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the molecular mechanisms by which Galectin-1 promotes the malignant behavior of pancreatic cancer cells remain unclear. In this study, we examined the effects of Galectin-1 knockdown or overexpression in PSCs co-cultured with pancreatic cancer (PANC-1) cells. Immunohistochemical analysis showed expression of epithelial-mesenchymal transition (EMT) markers and MMP9 were positively associated with the expression of Galectin-1 in 66 human PDAC tissues. In addition, our in vitro studies showed PSC-derived Galectin-1 promoted the proliferation, invasion, and survival (anti-apoptotic effects) of PANC-1 cells. We also showed PSC-derived Galectin-1 induced EMT of PANC-1 cells and activated the NF-кB pathway in vitro. Our mixed (PSCs and PANC-1 cells) mouse orthotopic xenograft model indicated that overexpression of Galectin-1 in PSCs significantly promoted the proliferation, growth, invasion, and liver metastasis of the transplanted tumor. Moreover, Galectin-1 overexpression in PSCs was strongly associated with increased expression of EMT markers in both the orthotopic xenograft tumor in the pancreas and in metastatic lesions of naked mice. We conclude that PSC-derived Galectin-1 promotes the malignant behavior of PDAC by inducing EMT via activation of the NF-κB pathway. Our results suggest that targeting Galectin-1 in PSCs could represent a promising therapeutic strategy for PDAC progression and metastasis.
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