PUBLICATION
Exosomal Thrombospondin-1 Disrupts the Integrity of Endothelial Intercellular Junctions to Facilitate Breast Cancer Cell Metastasis
- Authors
- Cen, J., Feng, L., Ke, H., Bao, L., Li, L.Z., Tanaka, Y., Weng, J., Su, L.
- ID
- ZDB-PUB-191212-18
- Date
- 2019
- Source
- Cancers 11(12): (Journal)
- Registered Authors
- Keywords
- breast cancer, endothelial intercellular junctions, exosome, thrombospondin-1 (TSP1), transendothelial migration
- MeSH Terms
- none
- PubMed
- 31817450 Full text @ Cancers
Citation
Cen, J., Feng, L., Ke, H., Bao, L., Li, L.Z., Tanaka, Y., Weng, J., Su, L. (2019) Exosomal Thrombospondin-1 Disrupts the Integrity of Endothelial Intercellular Junctions to Facilitate Breast Cancer Cell Metastasis. Cancers. 11(12):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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Orthology
Engineered Foreign Genes
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