Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins

Handle URI:
http://hdl.handle.net/10754/550074
Title:
Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins
Authors:
Chan, Yuk-kit; Zhang, Huoming ( 0000-0001-5416-0358 ) ; Liu, Pei; Tsao, George Sai-wah; Li Lung, Maria; Mak, Nai-ki; Ngok-shun Wong, Ricky; Ying-kit Yue, Patrick
Abstract:
Exosomes, a group of secreted extracellular nanovesicles containing genetic materials and signaling molecules, play a critical role in intercellular communication. During tumorigenesis, exosomes have been demonstrated to promote tumor angiogenesis and metastasis while their biological functions in nasopharyngeal carcinoma (NPC) are poorly understood. In this study, we focused on the role of NPC-derived exosomes on angiogenesis. Exosomes derived from the NPC C666-1 cells and immortalized nasopharyngeal epithelial cells (NP69 and NP460) were isolated using ultracentrifugation. The molecular profile and biophysical characteristics of exosomes were verified by Western blotting, sucrose density gradient, and electron microscopy. We showed that the C666-1 exosomes (10 and 20 μg/ml) could significantly increase the tubulogenesis, migration and invasion of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Subsequently, an iTRAQ-based quantitative proteomics was used to identify the differentially expressed proteins in C666-1 exosomes. Among the 640 identified proteins, 51 and 89 proteins were considered as up- and down-regulated (≥ 1.5-fold variations) in C666-1 exosomes compared to the normal counterparts, respectively. As expected, pro-angiogenic proteins including intercellular adhesion molecule-1 (ICAM-1) and CD44 variant isoform 5 (CD44v5) are among the up-regulated proteins, whereas angio-suppressive protein, thrombospondin-1 (TSP-1) was down-regulated in C666-1 exosomes. Further confocal microscopic study and Western blotting clearly demonstrated that the alteration of ICAM-1, and TSP-1 expressions in recipient HUVECs are due to internalization of exosomes. Taken together, these data strongly indicated the critical roles of identified angiogenic proteins in the involvement of exosomes-induced angiogenesis, which could potentially be developed as therapeutic targets in future. This article is protected by copyright. All rights reserved.
KAUST Department:
Biosciences Core Lab
Citation:
Chan, Yuk‐kit, Huoming Zhang, Pei Liu, George Sai‐wah Tsao, Maria Li Lung, Nai‐ki Mak, Ngok‐shun Wong, and Ying‐kit Yue. "Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins." International Journal of Cancer (2015).
Journal:
International Journal of Cancer
Issue Date:
Apr-2015
DOI:
10.1002/ijc.29562
Type:
Article
ISSN:
00207136
Additional Links:
http://doi.wiley.com/10.1002/ijc.29562
Appears in Collections:
Articles; Biosciences Core Lab

Full metadata record

DC FieldValue Language
dc.contributor.authorChan, Yuk-kiten
dc.contributor.authorZhang, Huomingen
dc.contributor.authorLiu, Peien
dc.contributor.authorTsao, George Sai-wahen
dc.contributor.authorLi Lung, Mariaen
dc.contributor.authorMak, Nai-kien
dc.contributor.authorNgok-shun Wong, Rickyen
dc.contributor.authorYing-kit Yue, Patricken
dc.date.accessioned2015-04-14T12:49:42Zen
dc.date.available2015-04-14T12:49:42Zen
dc.date.issued2015-04en
dc.identifier.citationChan, Yuk‐kit, Huoming Zhang, Pei Liu, George Sai‐wah Tsao, Maria Li Lung, Nai‐ki Mak, Ngok‐shun Wong, and Ying‐kit Yue. "Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins." International Journal of Cancer (2015).en
dc.identifier.issn00207136en
dc.identifier.doi10.1002/ijc.29562en
dc.identifier.urihttp://hdl.handle.net/10754/550074en
dc.description.abstractExosomes, a group of secreted extracellular nanovesicles containing genetic materials and signaling molecules, play a critical role in intercellular communication. During tumorigenesis, exosomes have been demonstrated to promote tumor angiogenesis and metastasis while their biological functions in nasopharyngeal carcinoma (NPC) are poorly understood. In this study, we focused on the role of NPC-derived exosomes on angiogenesis. Exosomes derived from the NPC C666-1 cells and immortalized nasopharyngeal epithelial cells (NP69 and NP460) were isolated using ultracentrifugation. The molecular profile and biophysical characteristics of exosomes were verified by Western blotting, sucrose density gradient, and electron microscopy. We showed that the C666-1 exosomes (10 and 20 μg/ml) could significantly increase the tubulogenesis, migration and invasion of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Subsequently, an iTRAQ-based quantitative proteomics was used to identify the differentially expressed proteins in C666-1 exosomes. Among the 640 identified proteins, 51 and 89 proteins were considered as up- and down-regulated (≥ 1.5-fold variations) in C666-1 exosomes compared to the normal counterparts, respectively. As expected, pro-angiogenic proteins including intercellular adhesion molecule-1 (ICAM-1) and CD44 variant isoform 5 (CD44v5) are among the up-regulated proteins, whereas angio-suppressive protein, thrombospondin-1 (TSP-1) was down-regulated in C666-1 exosomes. Further confocal microscopic study and Western blotting clearly demonstrated that the alteration of ICAM-1, and TSP-1 expressions in recipient HUVECs are due to internalization of exosomes. Taken together, these data strongly indicated the critical roles of identified angiogenic proteins in the involvement of exosomes-induced angiogenesis, which could potentially be developed as therapeutic targets in future. This article is protected by copyright. All rights reserved.en
dc.relation.urlhttp://doi.wiley.com/10.1002/ijc.29562en
dc.rightsThis is the peer reviewed version of the following article: Chan, Yuk‐kit, Huoming Zhang, Pei Liu, George Sai‐wah Tsao, Maria Li Lung, Nai‐ki Mak, Ngok‐shun Wong, and Ying‐kit Yue. "Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins." International Journal of Cancer (2015), which has been published in final form at 10.1002/ijc.29562. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.en
dc.titleProteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteinsen
dc.typeArticleen
dc.contributor.departmentBiosciences Core Laben
dc.identifier.journalInternational Journal of Canceren
dc.eprint.versionPost-printen
dc.contributor.institutionDepartment of Biology, Faculty of Science; Hong Kong Baptist University; Hong Kong SARen
dc.contributor.institutionDepartment of Biology, Faculty of Science; Hong Kong Baptist University; Hong Kong SARen
dc.contributor.institutionDepartment of Anatomy; University of Hong Kong; Hong Kong SARen
dc.contributor.institutionDepartment of Clinical Oncology; University of Hong Kong; Hong Kong P.R. Chinaen
dc.contributor.institutionDepartment of Biology, Faculty of Science; Hong Kong Baptist University; Hong Kong SARen
dc.contributor.institutionDepartment of Biology, Faculty of Science; Hong Kong Baptist University; Hong Kong SARen
dc.contributor.institutionDepartment of Biology, Faculty of Science; Hong Kong Baptist University; Hong Kong SARen
dc.contributor.institutionCenter for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong SARen
kaust.authorZhang, Huomingen
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