CTC clusters induced by heparanase enhance breast cancer metastasis
Wei, Rong-rui1; Sun, Dan-ni2; Yang, Hong2; Yan, Juan2; Zhang, Xiong2; Zheng, Xing-ling2; Fu, Xu-hong2; Geng, Mei-yu2; Huang, Xun2; Ding, Jian2
刊名ACTA PHARMACOLOGICA SINICA
2018-08
卷号39期号:8页码:1326-1337
关键词human breast cancer CTC clusters heparanase metastasis cell adhesion adhesion molecules suspension culture method
ISSN号1671-4083
DOI10.1038/aps.2017.189
文献子类Article
英文摘要Aggregated metastatic cancer cells, referred to as circulating tumor cell (CTC) clusters, are present in the blood of cancer patients and contribute to cancer metastasis. However, the origin of CTC clusters, especially intravascular aggregates, remains unknown. Here, we employ suspension culture methods to mimic CTC cluster formation in the circulation of breast cancer patients. CTC clusters generated using these methods exhibited an increased metastatic potential that was defined by the overexpression of heparanase (HPSE). Heparanase induced FAK- and ICAM-1-dependent cell adhesion, which promoted intravascular cell aggregation. Moreover, knockdown of heparanase or inhibition of its activity with JG6, a heparanase inhibitor, was sufficient to block the formation of cell clusters and suppress breast cancer metastasis. Our data reveal that heparanase-mediated cell adhesion is critical for metastasis mediated by intravascular CTC clusters. We also suggest that targeting the function of heparanase in cancer cell dissemination might limit metastatic progression.
资助项目National Natural Science Foundation of China[81302791] ; Youth Innovation Promotion Association CAS[00000000] ; Chinese Academy of Sciences[XDA12020326] ; Shanghai Talent Development Funds[201663]
WOS关键词CIRCULATING TUMOR-CELLS ; FOCAL ADHESION KINASE ; INHIBITOR PI-88 ; LUNG-CANCER ; ANGIOGENESIS ; DISSEMINATION ; PLAKOGLOBIN ; MIGRATION ; MELANOMA ; SULFATE
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:6309897
出版者ACTA PHARMACOLOGICA SINICA
WOS记录号WOS:000441241700008
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/279633]  
专题药理学第一研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Huang, Xun; Ding, Jian
作者单位1.China Pharmaceut Univ, Dept New Drug Screening Ctr, Nanjing 210009, Jiangsu, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
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Wei, Rong-rui,Sun, Dan-ni,Yang, Hong,et al. CTC clusters induced by heparanase enhance breast cancer metastasis[J]. ACTA PHARMACOLOGICA SINICA,2018,39(8):1326-1337.
APA Wei, Rong-rui.,Sun, Dan-ni.,Yang, Hong.,Yan, Juan.,Zhang, Xiong.,...&Ding, Jian.(2018).CTC clusters induced by heparanase enhance breast cancer metastasis.ACTA PHARMACOLOGICA SINICA,39(8),1326-1337.
MLA Wei, Rong-rui,et al."CTC clusters induced by heparanase enhance breast cancer metastasis".ACTA PHARMACOLOGICA SINICA 39.8(2018):1326-1337.
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