New discovery about role of sugar in cell communication

May 9 2006

A research team from Uppsala University has uncovered an entirely new mechanism for how communication between cells is regulated.

By functioning like glue, a certain type of sugar in the body can make cell communication more effective and stimulate the generation of new blood vessels.

The discovery paves the way for the development of drugs for cancer and rheumatism, for example. The study is being published on May 9 in the prominent journal Developmental Cell.

Blood vessels are made up of tubes consisting of endothelial cells, support cells, and membranes in various layers. The inside of the vessel is covered with endothelial cells. Blood is transported throughout the body in blood vessels, providing tissues with oxygen and nourishment. To carry out this assignment and to form new blood vessels, it is necessary to have close contact and communication between the various cells and membranes of the blood vessels.

In order to study how cell communication regulates the new generation of blood cells, a research team from Uppsala University studied blood vessels grown from embryonic stem cells from mice. By genetic modification of the stem cells, these scientists can now show that the production of the sugar molecule heparan sulfate is an absolute requirement for the formation of blood vessels.

"We made use of stem cells with two types of genetic modifications. In the first we removed the gene that produces the enzyme needed for sugar chains to bind various growth factors. In the other modification we removed the gene that produces the receptor for the growth factor VEGF (vascular endothelial growth factor)," says Lars Jakobsson.

The first modification resulted in cells with defective heparan sulfate and the other in the cells' not being able to form the receptor for VEGF. Neither of these two types of stem cells was able to generate blood vessels on its own.

"To further study the role of heparan sulfate in cells, we developed a model in which we let the different stem cell modifications grow together. It turned out that under these conditions the cells were able to generate lots of blood vessels. This is highly surprising, and exciting. It provides us with new information about how various cells can communicate and support each other in forming various organs in the body," says Lars Jakobsson.

The new stem cell model makes it possible to create cultures in which heparan sulfate is produced solely by support cells and not by endothelial cells. It has previously been known that heparan sulfate binds various growth factors, including VEGF, and 'introduces' these factors to the receptors on the surface of the cell. The Uppsala researchers are now demonstrating that VEGF that is introduced by heparan sulfate to support cells (as opposed to the heparan sulfate found on endothelial cells) provides a much stronger and longer-lasting effect on the activation of endothelial cells. The conclusion is that both the amount and the position of the heparan sulfate play a decisive role in the formation of new blood vessels.

"We show that heparan sulfate serves as glue that holds VEGF and its receptors in place on the surface of the cell so that the signal to generate new blood vessels lingers much longer. It was not previously known that heparan sulfate has this function, and the function may very well apply to other systems of receptors and communication," Lars Jakobsson believes.

These scientists have thus identified an entirely new mechanism for how communication can be regulated between cells. This clears the way for the creation of new drugs that can regulate the new generation of blood vessels. Such drugs could improve the treatment of cancer, rheumatism, and certain eye disease, for instance.