Platelet-derived extracellular vesicles inhibit ferroptosis and promote distant metastasis of nasopharyngeal carcinoma by upregulating ITGB3
| Autor: | Fei Li, Ting Xu, Peiling Chen, Rui Sun, Chaoyi Li, Xin Zhao, Jinxin Ou, Jingyao Li, Taoshu Liu, Maozhen Zeng, Weizhong Zheng, Yunchen Lin, Le Yang, Zecang Li, Haisheng Chen, Qing Zhang |
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| Rok vydání: | 2022 |
| Předmět: |
Nasopharyngeal Carcinoma
NF-E2-Related Factor 2 Integrin beta3 Nasopharyngeal Neoplasms Cell Biology Applied Microbiology and Biotechnology Gene Expression Regulation Neoplastic Mice Extracellular Vesicles Cell Line Tumor Animals Humans Ferroptosis Neoplasm Metastasis Molecular Biology Ecology Evolution Behavior and Systematics Developmental Biology |
| Zdroj: | International Journal of Biological Sciences. 18:5858-5872 |
| ISSN: | 1449-2288 |
| DOI: | 10.7150/ijbs.76162 |
| Popis: | Nasopharyngeal carcinoma (NPC) is a malignancy with high metastatic and invasive nature. Distant metastasis contributes substantially to treatment failure and mortality in NPC. Platelets are versatile blood cells and the number of platelets is positively associated with the distant metastasis of tumor cells. However, the role and underlying mechanism of platelets responsible for the metastasis of NPC cells remain unclear. Here we found that the distant metastasis of NPC patients was positively correlated with the expression levels of integrin β3 (ITGB3) in platelet-derived extracellular vesicles (EVs) from NPC patients (P-EVs). We further revealed that EVs transfer occurred from platelets to NPC cells, mediating cell-cell communication and inducing the metastasis of NPC cells by upregulating ITGB3 expression. Mechanistically, P-EVs-upregulated ITGB3 increased SLC7A11 expression by enhancing protein stability and activating the MAPK/ERK/ATF4/Nrf2 axis, which suppressed ferroptosis, thereby facilitating the metastasis of NPC cells. NPC xenografts in mouse models further confirmed that P-EVs inhibited the ferroptosis of circulating NPC cells and promoted the distant metastasis of NPC cells. Thus, these findings elucidate a novel role of platelet-derived EVs in NPC metastasis, which not only improves our understanding of platelet-mediated tumor distant metastasis, but also has important implications in diagnosis and treatment of NPC. |
| Databáze: | OpenAIRE |
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