Pancreatic cancer-derived exosomes promote tumor metastasis and liver pre-metastatic niche formation
| Autor: | Susu Zhao, Zhangjun Chen, Robert M. Hoffman, Lishan Wang, Zeqian Yu, Long Ren, Jiahua Zhou |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty pre-metastatic niche business.industry pancreatic cancer Cancer exosomes medicine.disease Proteomics Primary tumor Microvesicles Metastasis 03 medical and health sciences proteomics 030104 developmental biology iTRAQ Oncology Cell culture Pancreatic cancer medicine Cancer research Signal transduction business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.18831 |
| Popis: | // Zeqian Yu 1, 2 , Susu Zhao 3 , Long Ren 1 , Lishan Wang 1 , Zhangjun Chen 1, 2 , Robert M. Hoffman 4, 5 and Jiahua Zhou 1, 2 1 Department of Hepatic-Biliary-Pancreatic Center, Zhongda Hospital, Southeast University, Nanjing, China 2 Department of Hepatobiliary Surgery Research Institute, Southeast University, Nanjing, China 3 Department of Pathology, Traditional Chinese Medicine Hospital of Jiangsu Province, Nanjing, China 4 Department of Surgery, University of California at San Diego, San Diego, California, USA 5 AntiCancer, Inc., San Diego, California, USA Correspondence to: Jiahua Zhou, email: zhoujh@seu.edu.cn Keywords: pancreatic cancer, exosomes, pre-metastatic niche, proteomics, iTRAQ Received: March 31, 2017 Accepted: June 01, 2017 Published: June 28, 2017 ABSTRACT 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 naive 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. |
| Databáze: | OpenAIRE |
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