Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived stem cell factor

doi:10.7554/eLife.97201

科研成果详情

题名	Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived stem cell factor
作者	Mao, Chenchen1,2,3; Chen, Yanyu2,3,4; Xing, Dong3; Zhang, Teming3; Lin, Yangxuan5; Long, Cong3; Yu, Jiaye3; Luo, Yunhui3; Ming, Tao3; Xie, Wangkai 3; Han, Zheng3; Mei, Dianfeng3; Xiang, Dan3; Lu, Mingdong1,2; Shen, Xian6; Xue, Xiangyang1,2,3
发表日期	2024-10-10
发表期刊	eLife 影响因子和分区
语种	英语
原始文献类型	Article
关键词	single-cell RNA-sequencing spatial transcriptomics colon cancer liver metastasis natural killer cells
其他关键词	COLORECTAL-CANCER ; RECEPTOR
摘要	The abundance and biological contribution of natural killer (NK) cells in cancer are controversial. Here, we aim to uncover clinical relevance and cellular roles of NK cells in colon cancer liver metastasis (CCLM). Here, we integrated single-cell RNA-sequencing, spatial transcriptomics (ST), and bulk RNA-sequencing datasets to investigate NK cells' biological properties and functions in the microenvironment of primary and liver metastatic tumors. Results were validated through an in vitro co-culture experiment based on bioinformatics analysis. Useing single-cell RNA-sequencing and ST, we mapped the immune cellular landscape of colon cancer and well-matched liver metastatic cancer. We discovered that GZMK+ resting NK cells increased significantly in tumor tissues and were enriched in the tumor regions of both diseases. After combining bulk RNA and clinical data, we observed that these NK cell subsets contributed to a worse prognosis. Meanwhile, KIR2DL4+ activated NK cells exhibited the opposite position and relevance. Pseudotime cell trajectory analysis revealed the evolution of activated to resting NK cells. In vitro experiments further confirmed that tumor-cell-co-cultured NK cells exhibited a decidual-like status, as evidenced by remarkable increasing CD9 expression. Functional experiments finally revealed that NK cells exhibited tumor-activating characteristics by promoting the dissociation of SCF (stem cell factor) on the tumor cells membrane depending on cell-to-cell interaction, as the supernatant of the co-culture system enhanced tumor progression. In summary, our findings revealed resting NK cells exhibited a clinical relevance with CCLM, which may be exploited for novel strategies to improve therapeutic outcomes for patients with CCLM.
资助项目	National Natural Science Foundation of China; Zhejiang Key Laboratory of New Techniques for Diagnosis and Treatment of Critical Diseases of Pancreas and Liver and Zhejiang International science and Technology Cooperation base for tumor transformation research
出版者	eLIFE SCIENCES PUBL LTD
ISSN	2050-084X
卷号	13
DOI	10.7554/eLife.97201
页数	23
WOS类目	Biology
WOS研究方向	Life Sciences & Biomedicine - Other Topics
WOS记录号	WOS:001337069400001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39387546
SCOPUSEID	2-s2.0-85206122928
通讯作者地址	[Lu, Mingdong;Xue, Xiangyang]Wenzhou Med Univ, Affiliated Hosp 2, Dept Gen Surg, Wenzhou, Peoples R China. ; [Lu, Mingdong;Xue, Xiangyang]Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Peoples R China. ; [Xiang, Dan;Xue, Xiangyang]Wenzhou Med Univ, Inst Mol Virol & Immunol, Sch Basic Med Sci, Dept Microbiol & Immunol, Wenzhou, Peoples R China. ; [Shen, Xian]Wenzhou Med Univ, Affiliated Hosp 1, Dept Gen Surg, Wenzhou, Peoples R China.
Scopus学科分类	Neuroscience (all);Biochemistry, Genetics and Molecular Biology (all);Immunology and Microbiology (all)
SCOPUS_ID	SCOPUS_ID:85206122928
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/220804
专题	附属第二医院基础医学院（机能实验教学中心）附属第一医院第二临床医学院、附属第二医院、育英儿童医院附属第一医院_心胸外科基础医学院（机能实验教学中心）_病原生物学与免疫学系
通讯作者	Xiang, Dan; Lu, Mingdong; Shen, Xian; Xue, Xiangyang
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 2, Dept Gen Surg, Wenzhou, Peoples R China; 2.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Peoples R China; 3.Wenzhou Med Univ, Inst Mol Virol & Immunol, Sch Basic Med Sci, Dept Microbiol & Immunol, Wenzhou, Peoples R China; 4.Wenzhou Med Univ, Affiliated Hosp 2, Dept Pediat Thorac Surg, Wenzhou, Peoples R China; 5.Wenzhou Med Univ, Affiliated Hosp 1, Dept Thorac Surg, Wenzhou, Peoples R China; 6.Wenzhou Med Univ, Affiliated Hosp 1, Dept Gen Surg, Wenzhou, Peoples R China
第一作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 基础医学院（机能实验教学中心）; 病原生物学与免疫学系
通讯作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 基础医学院（机能实验教学中心）; 病原生物学与免疫学系; 附属第一医院
第一作者的第一单位	附属第二医院
推荐引用方式 GB/T 7714	Mao, Chenchen,Chen, Yanyu,Xing, Dong,et al. Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived stem cell factor[J]. eLife,2024,13.
APA	Mao, Chenchen., Chen, Yanyu., Xing, Dong., Zhang, Teming., Lin, Yangxuan., ... & Xue, Xiangyang. (2024). Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived stem cell factor. eLife, 13.
MLA	Mao, Chenchen,et al."Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived stem cell factor".eLife 13(2024).