Getting chemotherapy agents into solid tumors can be a challenge because high fluid pressure inside tumors makes it difficult for drugs to leave the bloodstream and attack their targets. But now researchers at the University of California, San Francisco Medical Center have discovered a new way to regulate the leakiness of blood vessels: blocking certain molecules surrounding blood vessels in mice can temporarily tweak their leakiness, enhancing flow of drugs to tumors. If scientists can mimic this effect in humans, the compounds could be given along with chemotherapy drugs or molecular imaging reagents to more effectively deliver them into tumor tissues.
The vessels that supply blood to tumors are leakier than those feeding healthy tissue, allowing fluid to accumulate. That triggers high fluid pressure inside tumors, which in turn hinders effective transit of drugs out of blood vessels and into the spaces between the tumor cells, explains Lisa Coussens, senior author of the study, published in Disease Models and Mechanisms.
Coussens's team discovered that targeting the collagen matrix around blood vessels can control their leakiness. By experimentally inhibiting or enhancing the activity of a number of candidate molecules involved in these processes, they found that an enzyme called matrix metalloproteinase 14 (MMP14) and transforming growth factor beta (TGFß) both work to stabilize blood vessels in "normal" tissues. Reducing the enzyme's activity or the amount of the growth factor, or preventing cells from interacting with the growth factor by blocking its receptor, all made healthy blood vessels leaky, and also enhanced leakage of molecules out of tumor vessels and into the tumors.
The vessels that supply blood to tumors are leakier than those feeding healthy tissue, allowing fluid to accumulate. That triggers high fluid pressure inside tumors, which in turn hinders effective transit of drugs out of blood vessels and into the spaces between the tumor cells, explains Lisa Coussens, senior author of the study, published in Disease Models and Mechanisms.
Coussens's team discovered that targeting the collagen matrix around blood vessels can control their leakiness. By experimentally inhibiting or enhancing the activity of a number of candidate molecules involved in these processes, they found that an enzyme called matrix metalloproteinase 14 (MMP14) and transforming growth factor beta (TGFß) both work to stabilize blood vessels in "normal" tissues. Reducing the enzyme's activity or the amount of the growth factor, or preventing cells from interacting with the growth factor by blocking its receptor, all made healthy blood vessels leaky, and also enhanced leakage of molecules out of tumor vessels and into the tumors.
