Several experiments suggested that

Several experiments suggested that CTCs could usespecific cell surface receptors, such as integrins, to initiallyadhere to the luminal walls of arterioles and capillaries incertain tissues.12 However, far more extensive evidence indicates that physical trapping within small vessels providesmost wandering CTCs with the first foothold within a tissue,1but the detailed process of this occurrence is still unclear.Recently, researchers detected the formation of plakoglobinmediated CTC clusters in the blood stream. These CTC clusters might help CTCs to survive and arrest at the vascularbifurcation in breast cancer metastasis.13 However, extensivedata show that CTCs are widely disseminating on an individual cellular basis and CTC clusters are rare in the circulation.1,13 Thus, revealing the mechanism of individual CTCssurvival and arrest in hematogenous metastasis is necessary.Various animal models have been applied to examine thebehaviors of CTCs in blood circulation,1,5,14–16 each has itsown advantages. However, none of them was able to revealthe whole picture of distal metastases formation from a circulating tumor cell, leaving the mechanism of individual CTCsarrest still controversial. Here, we established an experimentalmetastasis model using transparent zebrafish embryo(kdrl:eGFP; Casper mutant) to study the behavior of CTCs inblood circulation. Continuously confocal tracking astonishingly discovered a secondary morphological switch of theelongated intra-capillary CTCs back into a round shape.Genetic and pharmacological inhibition experiments indicated the necessity of the intra-capillary morphology switch(ICMS) for CTCs arrest. Further in vitro and in vivo intervention experiments identified a role of RhoA in the ICMS