The study sheds light on how cancer cells leave the blood vessels to travel to a new part of the body, using a technique that allows researchers to map how cancer cells interact and exchange information with cells that make up the blood vessels.
When tumor cells spread, they first enter the blood stream and grip onto the inner walls of blood vessels. The researchers found that the cancer cells control phosphorylation state of a receptor protein called EPHA2 in order to push their way out of the vessels. Researchers found decreased phosphorylation of a site in cancer cells upon endothelial contact.
Phosphorylation of this site was found to be critical for EPHA2-mediated inhibition of transendothelial migration. Furthermore, a highly metastatic breast cancer cell line that targets the lung exhibited altered phosphorylation dynamics at this site and had enhanced adhesion to and migration through endothelial cell monolayers in culture.
When cancer cells interact with the walls of the blood vessels, EPHA2 is activated and the tumor cells remain inside the blood vessels. When the EPHA2 is inactive, the tumor cells can push out and spread.
"The next step is to figure out how to keep this receptor switched on, so that the tumour cells can't leave the blood vessels - stopping breast cancer spreading and making the disease easier to treat successfully" says the lead author.