| First Author | Lee CM | Year | 2022 |
| Journal | Int J Mol Sci | Volume | 23 |
| Issue | 7 | PubMed ID | 35408794 |
| Mgi Jnum | J:337125 | Mgi Id | MGI:7262097 |
| Doi | 10.3390/ijms23073433 | Citation | Lee CM, et al. (2022) Thrombin-Activated Platelets Protect Vascular Endothelium against Tumor Cell Extravasation by Targeting Endothelial VCAM-1. Int J Mol Sci 23(7) |
| abstractText | When activated by thrombin, the platelets release their granular store of factors. These thrombin-activated platelets (TAPLT) have been shown to be capable of ameliorating pro-inflammatory processes. In this study, we tested if TAPLT could also protect the endothelium against tumor-related pro-inflammatory changes that promote angiogenesis and metastasis. Using endothelial cell (EC) models in vitro, we demonstrated that TAPLT protected EC against tumor conditioned medium (TCM)-induced increases of reactive oxygen species (ROS) production, EC permeability and angiogenesis, and inhibited transendothelial migration that was critical for cancer cell extravasation and metastasis. In vivo observations of TAPLT-mediated inhibition of angiogenesis and pulmonary colonization in a BALB/c nude mouse model were consistent with the in vitro findings. Neutralization of vascular cell adhesion molecule-1 (VCAM-1) binding significantly inhibited the ability of TAPLT to interact with EC and abrogated the TAPLT-mediated protection of EC against tumor angiogenesis and metastasis. Taken together, these findings suggest that VCAM-1-mediated linkage to EC is required for TAPLT to confer protection of EC against tumor-induced permeation and angiogenesis, thereby resisting tumor extravasation and metastasis. |
