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

TitleProteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins
Authors
KeywordsAngiogenesis
Exosomes
iTRAQ
Nasopharyngeal carcinoma
Proteomic
Issue Date2015
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal of Cancer, 2015, v. 137 n. 8, p. 1830-1841 How to Cite?
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. What's new? Many cells secrete exosomes. These nanoscale vesicles contain signaling molecules, mRNA, and miRNA, and play a critical role in intercellular communication. In this study, the authors identified several angiogenic factors in exosomes from nasopharyngeal carcinoma (NPC) cells. Purified NPC exosomes also caused normal endothelial cells to change to an angiogenic phenotype. These findings shed new light on the mechanisms by which NPC tumors may increase their blood supply, and also suggest that these exosomes may offer a promising therapeutic target. © 2015 UICC.
Persistent Identifierhttp://hdl.handle.net/10722/211612
ISSN
2023 Impact Factor: 5.7
2023 SCImago Journal Rankings: 2.131
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, YK-
dc.contributor.authorZhang, HM-
dc.contributor.authorLiu, P-
dc.contributor.authorTsao, GSW-
dc.contributor.authorLung, ML-
dc.contributor.authorMak, NK-
dc.contributor.authorWong, RN-
dc.contributor.authorYue, PY-
dc.date.accessioned2015-07-21T02:04:44Z-
dc.date.available2015-07-21T02:04:44Z-
dc.date.issued2015-
dc.identifier.citationInternational Journal of Cancer, 2015, v. 137 n. 8, p. 1830-1841-
dc.identifier.issn0020-7136-
dc.identifier.urihttp://hdl.handle.net/10722/211612-
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. What's new? Many cells secrete exosomes. These nanoscale vesicles contain signaling molecules, mRNA, and miRNA, and play a critical role in intercellular communication. In this study, the authors identified several angiogenic factors in exosomes from nasopharyngeal carcinoma (NPC) cells. Purified NPC exosomes also caused normal endothelial cells to change to an angiogenic phenotype. These findings shed new light on the mechanisms by which NPC tumors may increase their blood supply, and also suggest that these exosomes may offer a promising therapeutic target. © 2015 UICC.-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home-
dc.relation.ispartofInternational Journal of Cancer-
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc.-
dc.rightsSpecial Statement for Preprint only Before publication: 'This is a preprint of an article accepted for publication in [The Journal of Pathology] Copyright © ([year]) ([Pathological Society of Great Britain and Ireland])'. After publication: the preprint notice should be amended to follows: 'This is a preprint of an article published in [include the complete citation information for the final version of the Contribution as published in the print edition of the Journal]' For Cochrane Library/ Cochrane Database of Systematic Reviews, add statement & acknowledgement : ‘This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 20XX, Issue X. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.’ Please include reference to the Review and hyperlink to the original version using the following format e.g. Authors. Title of Review. Cochrane Database of Systematic Reviews 20XX, Issue #. Art. No.: CD00XXXX. DOI: 10.1002/14651858.CD00XXXX (insert persistent link to the article by using the URL: http://dx.doi.org/10.1002/14651858.CD00XXXX) (This statement should refer to the most recent issue of the Cochrane Database of Systematic Reviews in which the Review published.)-
dc.subjectAngiogenesis-
dc.subjectExosomes-
dc.subjectiTRAQ-
dc.subjectNasopharyngeal carcinoma-
dc.subjectProteomic-
dc.titleProteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins-
dc.typeArticle-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.authorityLung, ML=rp00300-
dc.identifier.doi10.1002/ijc.29562-
dc.identifier.pmid25857718-
dc.identifier.scopuseid_2-s2.0-84938952292-
dc.identifier.hkuros244769-
dc.identifier.volume137-
dc.identifier.issue8-
dc.identifier.spage1830-
dc.identifier.epage1841-
dc.identifier.isiWOS:000359350600011-
dc.publisher.placeUnited States-
dc.identifier.issnl0020-7136-

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