RT Journal Article
SR Electronic
T1 Intravascular arrest of circulating tumor cells is a two-step process exploiting their adhesion repertoire
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 443374
DO 10.1101/443374
A1 Naël Osmani
A1 Gautier Follain
A1 Maria Jesus Garcia-Leon
A1 Olivier Lefebvre
A1 Sébastien Harlepp
A1 Jacky G. Goetz
YR 2018
UL http://biorxiv.org/content/early/2018/10/16/443374.abstract
AB Cancer metastasis is a process in which a primary tumor spreads to form life-threatening metastases. Circulating tumor cells (CTCs) may arrest in distant organs and escape by crossing the endothelial barrier. We have previously demonstrated that blood flow controls sequential CTC arrest and stable adhesion to endothelial cells. We now aim at identifying the adhesion receptors involved in each step. Early arrest is mediated by the formation of adhesion of weak magnitude of forces depending on CD44 and integrin αvβ3. Stabilization of this arrest uses integrin α5β1 dependent adhesions with larger magnitude of forces, which allows arrested CTCs to resist the shear forces conveyed by the blood flow. Finally, blood flow favors luminal deposition of fibronectin by endothelial cells, an integrin α5β1 ligand. In conclusion, we identified the molecular partners that are sequentially exploited by CTCs to arrest in vascular regions with permissive flow regimes, before extravasation.