When Soda peered at the tumor cells, he found--much to his surprise--that about 30 percent of vascular endothelial cells--specialized cells that line the interior surface of blood vessels--appeared green. "This indicated to us that they most likely originated from tumor cells," he says.

Further experiments revealed that TDECs, short for tumor-derived endothelial cells, are not specific to mouse tumors but can also be found in clinical samples taken from human glioblastoma patients. "This was really strong evidence for us that glioblastoma cells routinely transdifferentiate into endothelial cells," he explains.

The transformation is triggered by hypoxia, or low oxygen levels, which signals tumor cells that the time has come to start their shape-shifting stunt. But unlike regular vascular endothelial cells, TDECs don't require VEGF to form functional blood vessels. "This might explain why, despite being initially successful, anti-angiogenic therapy ultimately fails in glioblastomas," says Verma.

Avastin interrupts normal blood vessels, but eventually they are replaced with tumor-derived vessels, which are now treatment-resistant. "Once again, we are confronted with the versatility of tumor cells, which allows them to survive and thrive under adverse conditions," says Verma. "But as we learn more about tumors' molecular flexibility, we will be able to design novel, tailor-made combination therapies to combat deadly brain tumors."

SOURCE Salk Institute for Biological Studies