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

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. What's new? Stable arrest in capillaries is important for the survival of circulating tumor cells (CTCs) and is a prerequisite for extravasation and forming of distant metastases. Live tracking has however been a major challenge for tumor metastasis research. Using transparent transgenic zebrafish and resonant laser scanning confocal microscopy, here the authors tracked the fate of CTCs for days. The intra‐capillary morphology‐switch (ICMS) of individual CTCs from strip to sphere was necessary for their intravascular arrests. Further in vitro and in vivo intervention experiments identified a role of RhoA in the ICMS, suggesting the use of specific RhoA inhibitors in future treatments.