Scientists find key to blood vessel 'sprouting' and stability

Cancer Research UK

Cancer Research UK scientists have identified a network of proteins crucial for kick-starting the growth and stability of new blood vessels, reveals research published in Developmental Cell* today (Tuesday).

New blood vessels in tumours form by 'sprouting' - like the way branches grow on trees. Tumours feed off essential nutrients from the blood, supplied through these new vessels.

Now, scientists have discovered that a network of proteins - called the Wnt pathway - controls the stability of newly formed blood vessels. This determines whether or not they will survive to feed growing tissues with vital nutrients from the blood. Blocking the Wnt pathway in cells interferes with a crucial 'survival pathway' for newly formed blood vessels.

This discovery could enable scientists to develop drugs that not only stop new blood vessels from growing, but that will help to dismantle existing blood vessels in growing tumours. This two-pronged approach promises to be more effective than just stopping new blood vessels from growing.

Lead author Dr Holger Gerhardt, based at Cancer Research UK's London Research Institute, said: "Our findings open a new window of possibilities for understanding how blood vessels are 'pruned' away during normal development of a blood vessel network, and how to stop vessel loss in disease. This is particularly good news for cancer drug development as we hope to find more effective ways to cut the blood supply to tumours.

"Blood vessel stability is an important part of the formation of a tumour. In fact, recent studies show that the stability and quality of tumour blood vessels is more important than the density of blood vessels in tumour growth. Interestingly, the Wnt pathway is overactive in some cancers, suggesting we may be able to stop the growth of a tumour and its supporting blood vessels using one single approach."

The team of scientists studied the effects of mice deficient in a protein called Nrarp. They discovered that Nrarp was crucial for maintaining the connective arms of newly formed blood vessels. Before now, it was thought that cells surrounding blood vessels - called pericytes - were responsible for maintaining the stability of their connections. But this study shows that Nrarp functions within the blood vessels themselves by supporting the Wnt pathway to control vessel survival.

Scientists had previously discovered that the Nrarp protein can activate the Wnt pathway in some organs. With the new knowledge that Nrarp is involved in blood vessel 'pruning', further investigation revealed that inhibiting the Wnt pathway could lead to newly formed blood vessels quickly dying out.

Dr Richard Treisman, director of Cancer Research UK's London Research Institute, said: "Tumours feed off essential nutrients from the blood supply, so research into how to block this is a crucial area of cancer research.

"This interesting finding adds a lot to our understanding of this important process and will help other researchers working in this field."

ENDS

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Notes to Editor

* Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis. Phng et al. Developmental Cell. 20 Jan 2009.

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