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A novel mouse model for liver metastasis of prostate cancer reveals dynamic tumour-immune cell communication

文献类型：期刊论文

作者Liu, Kaiyuan1; Jing, Na1,2,3; Wang, Deng1,2,3; Xu, Penghui1; Wang, Jinming1; Chen, Xinyu1; Cheng, Chaping1; Xin, Zhixiang1; He, Yuman1; Zhao, Huifang1
刊名CELL PROLIFERATION
出版日期2021-05-21
页码12
关键词liver metastasis metastasis‐ associated immune cell metastatic microenvironment prostate cancer
ISSN号0960-7722
DOI10.1111/cpr.13056
通讯作者Zhu, Helen He(zhuhecrane@shsmu.edu.cn) ; Zhang, Kai(zhangkai@alumni.sjtu.edu.cn)
英文摘要Objectives In contrast to extensive studies on bone metastasis in advanced prostate cancer (PCa), liver metastasis has been under-researched so far. In order to decipher molecular and cellular mechanisms underpinning liver metastasis of advanced PCa, we develop a rapid and immune sufficient mouse model for liver metastasis of PCa via orthotopic injection of organoids from PbCre(+); rb1(f/f);p53(f/f) mice. Materials and Methods PbCre(+);rb1(f/f);p53(f/f) and PbCre(+);pten(f/f);p53(f/f) mice were used to generate PCa organoid cultures in vitro. Immune sufficient liver metastasis models were established via orthotopic transplantation of organoids into the prostate of C57BL/6 mice. Immunofluorescent and immunohistochemical staining were performed to characterize the lineage profile in primary tumour and organoid-derived tumour (ODT). The growth of niche-labelling reporter infected ODT can be visualized by bioluminescent imaging system. Immune cells that communicated with tumour cells in the liver metastatic niche were determined by flow cytometry. Results A PCa liver metastasis model with full penetrance is established in immune-intact mouse. This model reconstitutes the histological and lineage features of original tumours and reveals dynamic tumour-immune cell communication in liver metastatic foci. Our results suggest that a lack of CD8(+) T cell and an enrichment of CD163(+) M2-like macrophage as well as PD1(+)CD4(+) T cell contribute to an immuno-suppressive microenvironment of PCa liver metastasis. Conclusions Our model can be served as a reliable tool for analysis of the molecular pathogenesis and tumour-immune cell crosstalk in liver metastasis of PCa, and might be used as a valuable in vivo model for therapy development.
WOS关键词MICROENVIRONMENT ; PERSPECTIVES ; PROGENITORS
资助项目National Key R&D Program of China[2017YFA0102900] ; National Natural Science Foundation of China[NSFC32022021] ; National Natural Science Foundation of China[NSFC81772743] ; National Natural Science Foundation of China[NSFC81972404] ; Higher Education Discipline Innovation Project[B21024] ; Shanghai Municipal Education Commission-Gaofeng Clinical Medicine[20181706] ; Innovative Research Team of High-level Local Universities in Shanghai
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000652756300001
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/297335]  
专题新药研究国家重点实验室
通讯作者Zhu, Helen He; Zhang, Kai
作者单位1.Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Renji Med X Stem Cell Res Ctr, Ren Ji Hosp,Sch Med, Shanghai, Peoples R China
2.Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai, Peoples R China
3.Shanghai Jiao Tong Univ, Med X Res Inst, Shanghai, Peoples R China
4.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Kaiyuan,Jing, Na,Wang, Deng,et al. A novel mouse model for liver metastasis of prostate cancer reveals dynamic tumour-immune cell communication[J]. CELL PROLIFERATION,2021:12.
APA Liu, Kaiyuan.,Jing, Na.,Wang, Deng.,Xu, Penghui.,Wang, Jinming.,...&Zhang, Kai.(2021).A novel mouse model for liver metastasis of prostate cancer reveals dynamic tumour-immune cell communication.CELL PROLIFERATION,12.
MLA Liu, Kaiyuan,et al."A novel mouse model for liver metastasis of prostate cancer reveals dynamic tumour-immune cell communication".CELL PROLIFERATION (2021):12.

入库方式： OAI收割

来源：上海药物研究所

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