PUBLICATION
RhoA-stimulated Intra-capillary Morphology Switch Facilitates the Arrest of Individual Circulating Tumor Cells
- Authors
- Huang, X., Yang, Y., Zhao, Y., Dan, C., Ai, X., Zeng, A., Gou, M., Cai, L., Yang, H., Zhao, C.
- ID
- ZDB-PUB-171227-2
- Date
- 2017
- Source
- International Journal of Cancer 142(10): 2094-2105 (Journal)
- Registered Authors
- Keywords
- CTCs arrest, RhoA, hematogenous metastasis
- MeSH Terms
-
- Actin Cytoskeleton
- Animals
- Animals, Genetically Modified
- Capillaries/metabolism
- Capillaries/pathology*
- Colonic Neoplasms/metabolism
- Colonic Neoplasms/pathology
- Disease Models, Animal
- Mammary Neoplasms, Experimental/metabolism
- Mammary Neoplasms, Experimental/pathology
- Melanoma, Experimental/metabolism
- Melanoma, Experimental/pathology
- Mice
- Neoplasms, Experimental/metabolism
- Neoplasms, Experimental/pathology*
- Neoplastic Cells, Circulating/metabolism
- Neoplastic Cells, Circulating/pathology*
- Zebrafish
- rhoA GTP-Binding Protein/antagonists & inhibitors
- rhoA GTP-Binding Protein/metabolism*
- PubMed
- 29277889 Full text @ Int. J. Cancer
Citation
Huang, X., Yang, Y., Zhao, Y., Dan, C., Ai, X., Zeng, A., Gou, M., Cai, L., Yang, H., Zhao, C. (2017) RhoA-stimulated Intra-capillary Morphology Switch Facilitates the Arrest of Individual Circulating Tumor Cells. International Journal of Cancer. 142(10):2094-2105.
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. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping