期刊
INTERNATIONAL JOURNAL OF CANCER
卷 142, 期 10, 页码 2094-2105出版社
WILEY
DOI: 10.1002/ijc.31238
关键词
RhoA; CTCs arrest; hematogenous metastasis
类别
资金
- National Natural Science Foundation of China [81502522, 81402275, 81500153, 81422025]
- China Postdoctoral Science Foundation [58-2549]
- CSCO-Merck Serono Oncology Research Fund [Y-MX2015-018]
Metastasis is the primary cause of death for most cancer patients. Hematogenous arrest of circulating tumor cells (CTCs) is an essential prerequisite for metastases formation. Using transparent transgenic zebrafish (kdrl:eGFP; Casper), together with resonant laser scanning confocal microscopy, we tracked the fate of CTCs in vivo in the blood circulation for days. We found the intra-capillary morphology-switch (ICMS) of individual CTCs from strip to sphere was necessary for their intravascular arrests. Further genetic and pharmacological inhibition experiments indicated that the RhoA signaling was necessary for ICMS and the arrest of CTCs. At last, we demonstrated that early treatment by a clinically approved RhoA/ROCK inhibitor, Fasudil, could efficiently inhibit the initial arrest of individual CTCs and reduce the incidence of tumor metastasis in both zebrafish and mouse models. These results together indicate that RhoA-stimulated ICMS represents a mechanism for the arrest of individual CTCs, providing a potential target for future treatments of hematogenous metastatic disease.
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