Brain and blood vessels share cues.

Researchers have unexpectedly found that as blood vessel cells grow, they sport a surface protein also displayed by developing brain cells. The finding suggests that this protein, known to guide embryonic brain cells as they form connections, may also influence the route taken by new blood vessels. Curiously, cancer cells also exhibit the protein, called neuropilin-1.

Michael Klagsbrun of Children's Hospital in Boston and his colleagues made these discoveries while searching for cell surface proteins that respond to vascular endothelial growth factor (VEGF), a protein that aids the formation of blood vessels. Many tumors, for example, make VEGF, which helps them establish a blood supply to fuel their continued growth.

The investigators found a new VEGF-binding surface protein on blood vessel cells, the third isolated so far. Surprisingly, it turned out to be neuropilin-1, which had been thought to operate primarily in the developing brain. Axons--the long extensions formed by growing brain cells--display neuropilin-1, which reacts to proteins called semaphorins or collapsins, which serve as axonal stop signs. When art axon reaches a brain region containing semaphorins, its tip collapses and the axon moves off in a different direction.

Finding neuropilin-1 on blood vessel cells raises many intriguing questions, such as whether VEGF uses it to guide the direction of vessel growth. Klagsbrun's group has found that blood vessel cells with neuropilin-1 and another VEGF receptor move more readily toward the growth factor than do cells with just the second receptor. They report their findings in the March 20 Cell.

Might the stop signs of the embryonic brain also work on blood vessels? "We're wondering if there are negative cues [for blood vessel growth] and if collapsin-semaphorin could be one of them," says Klagsbrun. He and his colleagues are also trying to understand why tumors both secrete VEGF and display its binding partner, neuropilin-1. Compounds that interfere with their joining may help fight cancer, speculates Klagsbrun.