Role of microenvironmental periostin in pancreatic cancer progression
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Yang Liu1,*, Fan Li1,*, Feng Gao1, Lingxi Xing1, Peng Qin2, Xingxin Liang1, Jiajie Zhang1, Xiaohui Qiao1, Lizhou Lin1, Qian Zhao3 and Lianfang Du1
1Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200080, China
2Department of Instrument Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
3Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis and National Ministry of Education, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
*These authors contributed equally to this work
Lianfang Du, email: [email protected]
Qian Zhao, email: [email protected]
Keywords: periostin, pancreatic cancer, microenvironment, pancreatic stellate cells, EGFR
Received: March 17, 2016 Accepted: July 09, 2016 Published: August 23, 2016
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent desmoplastic reaction. Pancreatic stellate cells (PSCs) are the principal effector cells responsible for stroma production. Aberrant up-regulation of periostin expression has been reported in activated PSCs. In this study, we investigated the role of periostin and the mechanisms underlying its aberrant upregulation in PDAC. We used lentiviral shRNA and human recombinant periostin protein to down and up regulate periostin expression in vitro. Specific oncogenic signaling pathways such as EGFR-Akt and EGFR-Erk-c-Myc were assessed in vitro and in vivo. Tissue microarray immunohistochemical assays including 80 pancreatic cancer tissues and paired normal tissues were used to understand the function relationship between periostin expression and PDAC pathologic stage and overall survival. We found that periostin was strongly expressed in PSCs and the stroma of PDAC tumors. We also observed a significant decrease in proliferation, metastasis, and clonality of pancreatic cancer cells when co-cultured with supernatant of periostin shRNA-transfected PSCs. Specifically, the biological behavior of periostin correlated with EGFR-Akt and EGER-Erk-c-Myc signaling pathways. Moreover, increased periostin expression significantly associated with advanced disease stage and decreased survival rate in PDAC patients. Together, our findings provide novel insights into the role of microenvironmental periostin in pancreatic cancer progression, and periostin may serve as a prognostic biomarker for PDAC.
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