TY  - JOUR
AU  - WEI Rong-rui
AU  - SUN Dan-ni
AU  - YANG Hong
AU  - YAN Juan
AU  - ZHANG Xiong
AU  - ZHENG Xing-ling
AU  - FU Xu-hong
AU  - GENG Mei-yu
AU  - HUANG Xun
AU  - DING Jian
PY  - 2018
TI  - CTC clusters induced by heparanase enhance breast cancer metastasis
JF  - Acta Pharmacologica Sinica; Vol 39, No 8 (August 2018): Acta Pharmacologica Sinica
Y2  - 2018
KW  - 
N2  - 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
UR  - http://www.chinaphar.com/article/view/9831