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Int J Cancer. 2018 May 15;142(10):2094-2105. doi: 10.1002/ijc.31238. Epub 2018 Jan 19.

RhoA-stimulated intra-capillary morphology switch facilitates the arrest of individual circulating tumor cells.

Author information

1
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan, People's Republic of China.
2
Blood Research Laboratory, Chengdu blood Center, Sichuan, People's Republic of China.
3
Personalized Drug Therapy Key Laboratory of Sichuan Province, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Sichuan, People's Republic of China.

Abstract

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.

KEYWORDS:

CTCs arrest; RhoA; hematogenous metastasis

PMID:
29277889
DOI:
10.1002/ijc.31238
[Indexed for MEDLINE]
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