Blood vessels supply all parts of the body with blood, thereby delivering oxygen and nutrients and at the same time removing carbon dioxide and waste products. We study how blood vessels are formed and which factors control the process, positively or negatively.
All growing tissues, both healthy and diseased, require formation of new blood vessels, angiogenesis. In diseases such as cancer angiogenesis is increased whereas other conditions can be accompanied by suppressed angiogenesis and poor circulation. Therefore, there is a therapeutic need to be able to both create new vessels and to prevent new vessels from forming.
In adults normally no new blood vessels are formed, except during wound healing and in the female menstruation cycle. This means that usually angiogenesis is strictly controlled so that new vessels only are formed when they are needed. However, in several diseases, for instance cancer, psoriasis, retina alterations in the eye and inflammatory diseases, new vessels are also formed.
In tumors new vessels are formed to provide oxygen and nutrient to the tumor cells, which supports their growth. Blood vessels also allow for the tumor cells to spread to other parts of the body, to metastasize. Substances that control angiogenesis might therefore function as cancer inhibiting drugs.
The growth factor VEGF regulates angiogenesis
We are studying several factors that control angiogenesis. Blood vessels are mainly built up by cells called endothelial cells. Growth factors that affect the endothelial cells can make the cells start dividing or move, allowing for new vessels to be formed.
A very important blood vessel stimulation factor is called VEGF (Vascular Endothelial Growth Factor). VEGF binds to specific receptors on the surface of the endothelial cells. This binding results in a signal that is transferred to the receptor and then on to other proteins, eventually leading to cell division. We are examining how this signal transduction occurs, which proteins are involved and if it is possible to regulate.
We have found a substance that efficiently affects angiogenesis in tumors, and also metastasis in tumor models, and we are presently testing it in the laboratory.
Regulation of vessel permeability
A large project in the group focuses on how signal transduction regulates blood vessel permeability, i.e. how molecules and cells can pass from the blood to the surrounding tissues. Vessel permeability, which can be transient or permanent, can aggravate disease conditions and hamper therapies.