Brain Tumors Grow Their Own Blood Supply

Shape-shifters. Some cells within these mouse blood vessels 
developed from human brain tumor cells.

Tumors are notoriously hard to kill. Attack them with chemotherapy, and they develop drug resistance; surgically remove them, and they may have already metastasized to other parts of the body. Now scientists have found that tumors have yet another trick up their sleeve: They can create their own blood supply by morphing into blood vessels. The observations, reported by two separate teams online today in Nature, could explain why drugs designed to choke off blood to brain tumors often fail.

The researchers drew the link between tumor cells and blood vessel cells with a series of experiments on glioblastomas—fast-growing brain tumors that contain tufts of thin, abnormal blood vessels. Neurosurgeon and stem cell scientist Viviane Tabar and colleagues at Memorial Sloan-Kettering Cancer Center in New York City first took glioma samples from the operating room and looked for chromosomal abnormalities in the endothelial cells lining the tumor's blood vessels. They foundpatterns exactly like those in cells from the tumor itself, suggesting that at least some of the blood vessel cells came from the tumor.

The researchers then sorted glioma cells into different types using antibodies that stick to specific proteins on a cell's surface. They showed that the cells that give rise to blood vessels are an immature cancer cell, known as a stemlike cancer cell. Finally, the researchers injected these cancer stem cells into the brains of mice with weakened immune systems and then examined the blood vessels within the resulting tumors. The vessels stained positive for antibodies to human endothelial cells, again showing that some of the cells had to come from the tumor.

The bottom line: "There is plasticity within the tumor, and it can make its own blood vessels," says Tabar. She says that this could explain why cancer drugs aimed at choking off a tumor's blood supply by blocking growth signals, known as angiogenesis inhibitors, usually stop working within about 6 months. When her team added one of the antiangiogenesis drugs to a culture of the cancer cells, the drug stopped immature blood vessel cells from maturing but didn't block the stem cells from developing into the immature blood vessel cells. Because tumor cells are genetically unstable, they may easily find ways to bypass the antiangiogenesis drugs, Tabar says.

A separate team led by Ruggero De Maria at the Istituto Superiore di Sanità in Rome published a similar set of experiments today. Both teams suggest that combining antiangiogenesis drugs with another drug that stops the stem cells from maturing might be a way to overcome resistance in gliomas and perhaps other cancers.

Other papers have hinted that cancer cells might give rise to blood vessel cells, but the two studies reporting essentially the same result confirm that suspicion, says angiogenesis researcher David Cheresh of the University of California, San Diego. "These two papers will put the controversy to rest."