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 (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, CD105, and mapped to human chromosome 9q3. It has approximately 70% homology with type-III cell-surface receptor for transforming growth factor beta (TGF-beta). Recently CD105 has been reported to be the gene in patients with hereditary haemorrhagic telangiectasia. 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 radiotherapy 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.
Wang
J M
JM
Christie Hospital, Manchester, UK.
Kumar
S
S
van Agthoven
A
A
Kumar
P
P
Pye
D
D
Hunter
R D
RD
D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D015703:Antigens, CD; D002448:Cell Adhesion / Q000528:radiation effects; D002452:Cell Count / Q000528:radiation effects; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D048429:Cell Size / Q000528:radiation effects; D002478:Cells, Cultured; D004586:Electrophoresis; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000378:metabolism / Q000528:radiation effects*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011233:Precipitin Tests; D011956:Receptors, Cell Surface; D015854:Up-Regulation / Q000528:radiation effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1