IRRADIATION INDUCES UP-REGULATION OF E9 PROTEIN (CD105) IN HUMAN VASCULAR ENDOTHELIAL-CELLS

The use of MAb E-9 raised against tissue-cultured endothelial cells (E C) has shown marked heterogeneity in vascular EC lining the blood vess els 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 k Da. 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 pr otein has been assigned to a new cluster, CD105, and mapped to human c hromosome 9q3. It has approximately 70% homology with type-III cell-su rface receptor for transforming growth factor beta (TGF-beta). Recentl y CD105 has been reported to be the gene in patients with hereditary h aemorrhagic telangiectasia. We have examined the effects of radiation on its expression in normal human umbilical-vein endothelial cells (HU VEC) and brain-tumour-derived endothelial cells (BTEC). Irradiation in duced dose- and time-dependent up-regulation in the expression of the E-9 protein on the plasma membranes of EC, and also resulted in greate r increase in the expression of the E-9 protein in semi-confluent (pro liferating) as compared with confluent (non-proliferating) EC. It may well be that, following radiotherapy in cancer patients, E-9 protein i s also up-regulated. The presence of increased amounts of E-9 protein in EC makes it an attractive target in the control of angiogenesis, es pecially after radiotherapy in cancer patients. The time scale involve d 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 pr oduction and release of mitogenic factors (such as basic fibroblast gr owth factor) from irradiated EC. (C) 1995 Wiley-Liss, Inc.