Transendothelial migration of malignant cells plays an essential role in
tumor progression and
metastasis. The present study revealed that treating human umbilical vein endothelial cells (HUVECs) with exosomes derived from metastatic
breast cancer cells increased the number of
cancer cells migrating through the endothelial cell layer and impaired the tube formation of HUVECs. Furthermore, the expression of intercellular junction
proteins, including
vascular endothelial cadherin (
VE-cadherin) and
zona occluden-1 (ZO-1), was reduced significantly in HUVECs treated with
carcinoma-derived exosomes. Proteomic analyses revealed that thrombospondin-1 (TSP1) was highly expressed in
breast cancer cell MDA-MB-231-derived exosomes. Treating HUVECs with TSP1-enriched exosomes similarly promoted the transendothelial migration of malignant cells and decreased the expression of intercellular junction
proteins. TSP1-down regulation abolished the effects of exosomes on HUVECs. The migration of
breast cancer cells was markedly increased in a zebrafish in vivo model injected with TSP1-overexpressing
breast cancer cells. Taken together, these results suggest that
carcinoma-derived exosomal TSP1 facilitated the transendothelial migration of
breast cancer cells via disrupting the intercellular integrity of endothelial cells.