Matrix metalloproteinase 13‐containing exosomes promote nasopharyngeal carcinoma metastasis

• Published in: Cancer science Vol. 106; no. 12; pp. 1669 - 1677
• Main Authors: You, Yiwen, Shan, Ying, Chen, Jing, Yue, Huijun, You, Bo, Shi, Si, Li, Xingyu, Cao, Xiaolei
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-12-2015; John Wiley and Sons Inc
• Subjects: Angiogenesis; Blotting, Western; Cancer; Carcinoma; Cell adhesion & migration; Collagenase 3; Epithelial-Mesenchymal Transition - physiology; Exosomes; Exosomes - metabolism; Extracellular matrix; Grants; Head & neck cancer; Humans; Immunohistochemistry; Lymph nodes; Matrix metalloproteinase; Matrix Metalloproteinase 13 - metabolism; Membranes; Metalloproteinase; Metastases; Metastasis; microenvironment nasopharyngeal carcinoma; MMP13; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - blood supply; Nasopharyngeal Neoplasms - enzymology; Nasopharyngeal Neoplasms - pathology; Neoplasm Invasiveness; Neoplasm Metastasis; Neovascularization, Pathologic; Original; Pore size; Proteinase; Proteins; Real-Time Polymerase Chain Reaction; RNA, Small Interfering; siRNA; Transfection; Tumor cells; Tumor Microenvironment - physiology; Tumors; United States > US; China; Japan; MMP13; microenvironment nasopharyngeal carcinoma; Exosomes; metastasis
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12818

Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. Metastasis is the major cause of death in NPC patients. Increasing evidence indicates that exosomes play a pivotal role in promoting cancer metastasis by enhancing angiogenesis and ECM degradation. Matrix metalloproteinase 13 is an important kind of matrix proteinase that is often overexpressed in various tumors and increases the risk of metastasis. However, little is known about the potential role of MMP13‐containing exosomes in NPC. In this study, we found that MMP13 was overexpressed in NPC cells and exosomes purified from conditioned medium (CM) as well as NPC patients’ plasma. Transwell analysis revealed that MMP13‐containing exosomes facilitated the metastasis of NPC cells. Furthermore, siRNA inhibited the effect of MMP13‐containing exosomes on tumor cells metastasis as well as angiogenesis. The current findings provided novel insight into the vital role of MMP13‐containing exosomes in NPC progression which might offer unique insights for potential therapeutic strategies for NPC progressions.
This work proved that MMP13‐containning exosomes from NPC could mediate tumor microenvironment such as facilitating tumor cells migration and invasion by interaction with stromal HSF and HUVECs. Our findings provide important and unique insights into the pathogenesis of NPC and underscore the need to explore alternative therapeutic approaches to impair MMP‐driven mechanisms of tumor invasion and metastasis.