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Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins.
Chan, Yuk-Kit; Zhang, Huoming; Liu, Pei; Tsao, Sai-Wah; Lung, Maria Li; Mak, Nai-Ki; Ngok-Shun Wong, Ricky; Ying-Kit Yue, Patrick.
Afiliación
  • Chan YK; Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR.
  • Zhang H; Bioscience Core Laboratory, King Abdullah, University of Science and Technology, Saudi Arabia.
  • Liu P; Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR.
  • Tsao SW; Department of Anatomy, University of Hong Kong.
  • Lung ML; Center for Nasopharyngeal Carcinoma Research, University of Hong Kong.
  • Mak NK; Center for Nasopharyngeal Carcinoma Research, University of Hong Kong.
  • Ngok-Shun Wong R; Department of Clinical Oncology, University of Hong Kong.
  • Ying-Kit Yue P; Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong SAR.
Int J Cancer ; 137(8): 1830-41, 2015 Oct 15.
Article en En | MEDLINE | ID: mdl-25857718
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Nasofaríngeas / Proteómica / Proteínas Angiogénicas / Exosomas / Neovascularización Patológica Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Int J Cancer Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Nasofaríngeas / Proteómica / Proteínas Angiogénicas / Exosomas / Neovascularización Patológica Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Int J Cancer Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos