Blood vessels form an extensive, tree-like network of arteries, veins and capillaries that consists of a monolayer of endothelial cells enclosing the lumen, and mural cells, namely pericytes and vascular smooth muscle cells (vSMCs), that form the outer layers of the vessel wall. Pericytes make direct cell-cell contact with several ECs in their vicinity with the help of numerous long cellular processes and thought to play important roles in the stabilization and maturation of the vascular system. Pericyte are hard to study because they are scattered throughout capillary beds, relatively scarce and difficult to isolate.
Moreover, there is a lack of general markers that can identify all PCs and the existing reagents only seem to detect certain subsets of these cells.
Pericytes are not only important in the healthy organism but they also play roles in pathological processes. Interactions between pericytes and the endothelium are loose in tumors, which is thought to enhance the leakiness and fragility of intratumor blood vessels. Pericytes are of great interest for the normalization of tumor vessels, an approach that might enhance the effect of circulating chemotherapeutics, or, alternatively, the destabilization of vessels that are protected against anti-angiogenic treatment. Here, we plan to investigate the dynamic behavior, fate and expression profile of pericytes in animal models of cancer. Genetic approaches in mice will be used for these studies as well as the functional characterization of Notch signaling in the tumor vasculature.
Benedito R., Roca C., Sörensen I., Adams S., Gossler A., Fruttiger M.
and Adams R.H. The Notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. In press, 2009
Sörensen I., Adams R.H., Gossler A., Blood. DLL1 mediated Notch activation regulates endothelial identity in mouse fetal arteries. Blood, Jan 14. [Epub ahead of print] 2009
Abraham S. , Kogata N., Fässler R. and Adams R.H. The integrin
β1 subunit controls mural cell adhesion, spreading and blood vessel wall stability. Circ. Res. 1025:562-70, 2008
Roca C. and Adams R.H. Regulation of vascular morphogenesis by Notch signalling. Genes Dev. 21:2511-24, 2007
Adams R.H. and Alitalo K. Molecular regulation of angiogenesis and lymphangiogenesis. Nature Rev. Mol. Cell. Biol. 8:464-78, 2007
Foo S.S., Turner C.J., Adams S., Compagni A., Aubyn D., Kogata N., Lindblom P., Shani M., Zicha D. and Adams R.H. Ephrin-B2 controls cell motility and adhesion during blood-vessel-wall assembly.
Cell 124:161-173, 2006