Targeting cancer-derived extracellular vesicles by combining CD147 inhibition and tissue factor pathway inhibitor for the management of urothelial cancer cells

Cancer cells release small particles or vesicles, which have the potency to induce cancer cells to spread and grow. In this study, we focused on two molecules presented by cell-derived vesicles that might promote cancer cells spread: a clotting protein and a cell surface protein. We found that vesicles from bladder cancer cells that could spread had higher levels of these proteins than vesicles from cancer cells that could not spread. We also found that these vesicles could make cancer cells move about more, produce more of a substance that helps cancer cells spread, and invade other tissues. To counteract the cancer-promoting actions of vesicles, we examined the impact of combining a naturally occurring anti-clotting protein that can be released by medications derived from heparin. We found that the combination could stop the vesicles from making cancer cells move about more, produce more of the spreading substance, and invade other tissues. These findings suggest that combining the inhibitor with medications derived from heparin to induce the release of the anti-clotting protein might be a new way to treat bladder cancer.