When a tumour grows, new blood vessels are formed that supply the tumour with nutrients and oxygen. However, these vessels are often malfunctioning and fluids and other molecules leak out of the vessels. This results in edema in the tissues, which in turn makes it more difficult for drugs to reach into the tumour during cancer therapy. The malfunctioning vessels can also contribute to the spread of metastases from the tumour.
The leakage from the blood vessels is controlled by specific protein complexes that connect the cells in the blood vessel walls. By regulating these protein complexes, the cells are joined more or less tightly, which affects the leakage from the vessels.
Recent findings from Uppsala University show how a specific alteration of the protein complex in the vessel walls can reduce leakage, without affecting any other vessel functions.
The growth factor VEGFA functions as a signalling molecule, regulating the protein complexes in the blood vessel walls. One way of treating cancer is by inhibiting VEGFA, which decreases leakage and edema and improves the effects of chemo- and radiation therapy. However, VEGFA affects blood vessels in several ways and sustained anti-VEGFA therapy deteriorates vessel function and can cause increased metastasis.
‘The specific mutation that we have studied allowed us to examine one of the signalling pathways in which VEGFA is involved. An important finding was that mice with the mutated protein complex also showed a reduced spread of metastases. We, therefore, believe that a targeted inhibition of this specific signalling pathway, which controls how the cells in the vessel walls are connected, might work better as a cancer therapy than the more general VEGFA inhibition that is used today,’ says Lena Claesson-Welsh.
Li et al. VEGFR2 pY949 signalling regulates adherens junction integrity and metastatic spread. Nature Communications. 2016;7:11017 doi:10.1038/ncomms11017 [Article]