Research Papers:

Pancreatic cancer-derived exosomes promote tumor metastasis and liver pre-metastatic niche formation

Zeqian Yu, Susu Zhao, Long Ren, Lishan Wang, Zhangjun Chen, Robert M. Hoffman and Jiahua Zhou _

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Oncotarget. 2017; 8:63461-63483. https://doi.org/10.18632/oncotarget.18831

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Zeqian Yu1,2, Susu Zhao3, Long Ren1, Lishan Wang1, Zhangjun Chen1,2, Robert M. Hoffman4,5 and Jiahua Zhou1,2

1Department of Hepatic-Biliary-Pancreatic Center, Zhongda Hospital, Southeast University, Nanjing, China

2Department of Hepatobiliary Surgery Research Institute, Southeast University, Nanjing, China

3Department of Pathology, Traditional Chinese Medicine Hospital of Jiangsu Province, Nanjing, China

4Department of Surgery, University of California at San Diego, San Diego, California, USA

5AntiCancer, Inc., San Diego, California, USA

Correspondence to:

Jiahua Zhou, email: [email protected]

Keywords: pancreatic cancer, exosomes, pre-metastatic niche, proteomics, iTRAQ

Received: March 31, 2017     Accepted: June 01, 2017     Published: June 28, 2017


Exosomes play important roles in cell-cell communication, and are likely mediators of the metastatic cascade in cancer. This study examined the role of exosomes in pancreatic cancer cell adhesion, migration, and invasion. We isolated and purified exosomes from two isogenic pancreatic cancer cell lines with different metastatic potentials. Uptake of exosomes from highly metastatic Panc02-H7 cells decreased adhesion and increased migration and invasion capacity in weakly metastatic Panc02 cells in vitro. Exosomes from highly metastatic pancreatic cancer cells induced liver pre-metastatic niche formation in naïve mice and promoted primary tumor growth and liver metastasis in vivo. We identified 4,517 proteins in exosomes from Panc02 and Panc02-H7 cells via iTRAQ quantitative proteomic analyses, 79 of which were differentially expressed between the two cell lines. Bioinformatics analyses showed that most of the differentially expressed proteins were involved in pancreatic cancer growth, invasion, and metastasis, and that metabolism-related signaling pathways were involved in exosome-mediated intracellular communication. Further studies will be needed to determine whether these proteins are potential pancreatic cancer diagnostic/prognostic markers or novel therapeutic targets.

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