Irradiation induces Up‐regulation of E9 protein (CD105) in human vascular endothelial cells

Abstract

The use of MAb E‐9 raised against tissue‐cultured endothelial cells (EC) has shown marked heterogeneity in vascular EC lining the blood vessels of normal and tumour tissues. MAb E‐9 is human EC‐specific and the protein recognized by it is a homodimer with a molecular mass of 97 kDa. The E‐9 protein is resistant to treatment by 3 mM sodium periodate, but is sensitive to 10% trichloroacetic acid and 70% ethanol. E‐9 protein has been assigned to a new cluster, CD 105, and mapped to human chromosome 9q3. It has approximately 70% homology with type‐III cell‐surface receptor for transforming growth factor beta (TGF‐β). Recently CD 105 has been reported to be the gene in patients with hereditary haemorrhagic telangiecta‐sia. We have examined the effects of radiation on its expression in normal human umbilical‐vein endothelial cells (HUVEC) and brain‐tumour‐derived endothelial cells (BTEC). Irradiation induced dose‐and time‐dependent up‐regulation in the expression of the E‐9 protein on the plasma membranes of EC, and also resulted in greater increase in the expression of the E‐9 protein in semi‐confluent (proliferating) as compared with confluent (non‐proliferating) EC. It may well be that, following radio‐therapy in cancer patients, E‐9 protein is also up‐regulated. The presence of increased amounts of E‐9 protein in EC makes it an attractive target in the control of angiogenesis, especially after radiotherapy in cancer patients. The time scale involved in the up‐regulation of E‐9 protein following irradiation has led us to suggest that it may be a secondary event, the primary being the production and release of mitogenic factors (such as basic fibroblast growth factor) from irradiated EC.