The increased expression of adhesion molecules ICAM-3, E- and P-selectins on breast cancer endothelium.
Sequential interaction of neoplastic cells with the endothelium of tumour neovasculature is believed to be a significant step in tumour metastasis. Increasing evidence suggests that inducible endothelial adhesion molecules are intimately involved in this process. An immunohistochemical approach was used to examine the expression of adhesion molecules in 14 normal controls and a series of 64 invasive breast carcinomas. Endothelium in normal breast showed constitutive expression of PECAM (100 per cent), ICAM-2 (100 per cent), and P-selectin (64 per cent); variable and focal expression of ICAM-1 (71 per cent); and only weak staining for E-selectin (21 per cent). No ICAM-3 or VCAM-1 expression was observed. Similarly to normal breast endothelium, widespread and intense immunoreactivity on the endothelium of tumour-associated vessels was seen for PECAM (100 per cent), ICAM-1 (69 per cent), and ICAM-2 (95 per cent). In contrast to normal tissues, E- and P-selectins showed increased intensity of staining (52 and 67 per cent of cases, respectively) and expression of E- and P-selectins was more prominent at the tumour periphery. ICAM-3 expression was increased on tumour endothelium (15 per cent of cases), but in common with VCAM-1 (10 per cent) expression was focal. A previously unreported finding was the immunoreactivity of the neoplastic epithelial cells for the non-epithelial lineage markers ICAM-1 (34 per cent), ICAM-3 (10.9 per cent), PECAM (1.6 per cent), and E- and P-selectins (7 and 37 per cent of cases, respectively). These findings show that tumour endothelium displays significant heterogeneity and can assume a pro-inflammatory phenotype, probably as a result of cytokine stimulation. Upregulation of adhesion molecules might contribute to changes in invasive phenotype by promoting endothelial cell adhesion and angiogenesis, as well as forming a substratum for tumour cells to assemble and attract macrophages.
Fox
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SB
Department of Cellular Science and ICRF Molecular Oncology, John Radcliffe Hospital, University of Oxford, U.K.
Turner
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GD
Gatter
K C
KC
Harris
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AL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001940:Breast / Q000737:chemistry; D001943:Breast Neoplasms / Q000737:chemistry*; D015815:Cell Adhesion Molecules / Q000032:analysis*; D019040:E-Selectin / Q000032:analysis*; D004727:Endothelium / Q000737:chemistry; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D019007:P-Selectin / Q000032:analysis*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D019040:E-Selectin; C483616:ICAM3 protein, human; D009363:Neoplasm Proteins; D019007:P-Selectin