Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway

doi:10.7150/ijbs.70289

	Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway
	Zhang, Wei 2; Zheng, Xiaoxiao 3; Yu, Yisong 4; Zheng, Li 3; Lan, Jiahua 3; Wu, Ying 3; Liu, Hao 3; Zhao, An 1; Huang, Hang 5; Chen, Wei 3
刊名	INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
	2022
卷号	18
关键词	Tumor-derived exosomes Renal cell carcinoma (RCC) Macrophage polarization lncARSR STAT3
ISSN号	1449-2288
DOI	10.7150/ijbs.70289
通讯作者	Zhao, An(zhaoan@zjcc.org.cn) ; Huang, Hang(huanghang2017@163.com) ; Chen, Wei(viogro@163.com)
英文摘要	Tumor-derived exosomes play a pivotal role in regulating tumor progression by mediating crosstalk between tumor cells and immune cells such as macrophages within the tumor microenvironment. Macrophages can adopt two distinct polarization statuses and switch between M1 or M2 activation phenotypes in response to the different external stimuli. However, the role of tumor derived exosomes in the macrophage phenotypic switch and tumor development have not been elucidated in renal cell carcinoma (RCC). Here we found that high macrophage infiltration was associated with worse prognosis in RCC patients, therefore we propose our hypothesis that RCC derived exosomes might directly influence macrophage polarization and thus promote tumor progression. Both cell-based in vitro models and orthotopic transplantation in vivo tumor models were constructed and ELISA, flow cytometry, and macrophage functional studies were performed to investigate whether and how RCC-derived exosomes regulate macrophage polarization and tumor growth. The results found that these exosomes promote macrophage polarization, cytokine release, phagocytosis, angiogenesis, and tumor development. Further study revealed high amount of a recently discovered lncRNA called lncARSR in RCC-derived exosomes. Overexpression of lncARSR induced phenotypic and functional changes of macrophages in vitro and promoted tumor growth in vivo, while knockdown of lncARSR by siRNA disrupted the exosomes-mediated macrophage polarization. LncARSR interacts directly with miR-34/miR- 449 to increase STAT3 expression and mediate macrophage polarization in RCC cells. Together, RCC-derived exosomes facilitate the development of tumor through inducing macrophage polarization via transferring lncARSR, suggesting that RCC-derived exosomes, lncARSR and STAT3 are the potential therapeutic targets for treatment of RCC.
资助项目	Zhejiang Provincial Nature Science Foundation of China[LR20H160001] ; Zhejiang Provincial Nature Science Foundation of China[LY22H050005] ; Zhejiang Provincial Nature Science Foundation of China[LQ20H050001] ; Zhejiang Provincial Nature Science Foundation of China[LY20H160013] ; Key R&D projects of Zhejiang Province[2021C03012] ; Young Qihuang Scholar of National Administration of Traditional Chinese Medicine ; Zhejiang Provincial Ten Thousand Plan for Young Top Talents ; Training objects of health innovative talents of Zhejiang Health ; Natural Science Foundation of China[81972693] ; Natural Science Foundation of China[81802383] ; Natural Science Foundation of China[81972674] ; Natural Science Foundation of China[81973654] ; Natural Science Foundation of China[31900543] ; Natural Science Foundation of China[81602217] ; Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project[2020ZZ004] ; Key Project Co-constructed by Zhejiang Province and Ministry[WKJ-ZJ-1916]
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
语种	英语
出版者	IVYSPRING INT PUBL
WOS记录号	WOS:000831189100008
资助机构	Zhejiang Provincial Nature Science Foundation of China ; Key R&D projects of Zhejiang Province ; Young Qihuang Scholar of National Administration of Traditional Chinese Medicine ; Zhejiang Provincial Ten Thousand Plan for Young Top Talents ; Training objects of health innovative talents of Zhejiang Health ; Natural Science Foundation of China ; Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project ; Key Project Co-constructed by Zhejiang Province and Ministry
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/129097]
专题	中国科学院合肥物质科学研究院
通讯作者	Zhao, An; Huang, Hang; Chen, Wei
作者单位	1.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Dept Tumor Res Inst, 1 East Banshan Rd, Hangzhou 310022, Peoples R China 2.Tongde Hosp Zhejiang Prov, Dept Urol, Hangzhou 310012, Zhejiang, Peoples R China 3.Zhejiang Acad Tradit Chinese Med, Tongde Hosp Zhejiang Prov, Canc Inst Integrated Tradit Chinese & Western Med, Key Lab Canc Prevent & Therapy Combining Tradit C, 234 Gucui Rd, Hangzhou 310012, Zhejiang, Peoples R China 4.Zhejiang Chinese Med Univ, Coll Life Sci, Hangzhou 31001, Peoples R China 5.Wenzhou Med Univ, Affiliated Hosp 1, Dept Urol, Wenzhou 325000, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Wei,Zheng, Xiaoxiao,Yu, Yisong,et al. Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2022,18.
APA	Zhang, Wei.,Zheng, Xiaoxiao.,Yu, Yisong.,Zheng, Li.,Lan, Jiahua.,...&Chen, Wei.(2022).Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,18.
MLA	Zhang, Wei,et al."Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 18(2022).