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Int J Biol Sci 2022; 18(15):5858-5872. doi:10.7150/ijbs.76162 This issue Cite

Research Paper

Platelet-derived extracellular vesicles inhibit ferroptosis and promote distant metastasis of nasopharyngeal carcinoma by upregulating ITGB3

Fei Li1, Ting Xu1, Peiling Chen1, Rui Sun2,3, Chaoyi Li1, Xin Zhao1, Jinxin Ou1, Jingyao Li1, Taoshu Liu1, Maozhen Zeng1, Weizhong Zheng1, Yunchen Lin1, Le Yang1, Zecang Li1, Haisheng Chen1, Qing Zhang1,4✉

1. State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
2. Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
3. Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.
4. Institute of Sun Yat-sen University in Shenzhen, Shenzhen, China.

✉ Corresponding author: Qing Zhang, Ph.D, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, Guangdong, P. R. China. Tel: 86-20-84113988, 13903018911; E-mail: lsszqsysu.edu.cn

Citation:
Li F, Xu T, Chen P, Sun R, Li C, Zhao X, Ou J, Li J, Liu T, Zeng M, Zheng W, Lin Y, Yang L, Li Z, Chen H, Zhang Q. Platelet-derived extracellular vesicles inhibit ferroptosis and promote distant metastasis of nasopharyngeal carcinoma by upregulating ITGB3. Int J Biol Sci 2022; 18(15):5858-5872. doi:10.7150/ijbs.76162. https://www.ijbs.com/v18p5858.htm
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Abstract

Graphic abstract

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.

Keywords: nasopharyngeal carcinoma, platelets, extracellular vesicles, ferroptosis, ITGB3

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APA
Li, F., Xu, T., Chen, P., Sun, R., Li, C., Zhao, X., Ou, J., Li, J., Liu, T., Zeng, M., Zheng, W., Lin, Y., Yang, L., Li, Z., Chen, H., Zhang, Q. (2022). Platelet-derived extracellular vesicles inhibit ferroptosis and promote distant metastasis of nasopharyngeal carcinoma by upregulating ITGB3. International Journal of Biological Sciences, 18(15), 5858-5872. https://doi.org/10.7150/ijbs.76162.

ACS
Li, F.; Xu, T.; Chen, P.; Sun, R.; Li, C.; Zhao, X.; Ou, J.; Li, J.; Liu, T.; Zeng, M.; Zheng, W.; Lin, Y.; Yang, L.; Li, Z.; Chen, H.; Zhang, Q. Platelet-derived extracellular vesicles inhibit ferroptosis and promote distant metastasis of nasopharyngeal carcinoma by upregulating ITGB3. Int. J. Biol. Sci. 2022, 18 (15), 5858-5872. DOI: 10.7150/ijbs.76162.

NLM
Li F, Xu T, Chen P, Sun R, Li C, Zhao X, Ou J, Li J, Liu T, Zeng M, Zheng W, Lin Y, Yang L, Li Z, Chen H, Zhang Q. Platelet-derived extracellular vesicles inhibit ferroptosis and promote distant metastasis of nasopharyngeal carcinoma by upregulating ITGB3. Int J Biol Sci 2022; 18(15):5858-5872. doi:10.7150/ijbs.76162. https://www.ijbs.com/v18p5858.htm

CSE
Li F, Xu T, Chen P, Sun R, Li C, Zhao X, Ou J, Li J, Liu T, Zeng M, Zheng W, Lin Y, Yang L, Li Z, Chen H, Zhang Q. 2022. Platelet-derived extracellular vesicles inhibit ferroptosis and promote distant metastasis of nasopharyngeal carcinoma by upregulating ITGB3. Int J Biol Sci. 18(15):5858-5872.

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