Abstract
BackgroundThe endothelial adhesion molecule, vascular adhesion protein-1 (VAP-1, AOC3) promotes lymphocyte recruitment to tumours, although the contribution that VAP-1 makes to lymphocyte recruitment in human colorectal cancer (CRC) is unknown. VAP-1 exists in circulating soluble form (sVAP-1). A previous study demonstrated elevated sVAP-1 levels in CRC patients. The aim of this study was to confirm this finding and study the differences in tissue VAP-1 expression between CRC and healthy tissues.MethodssVAP-1 levels were measured in the serum of 31 patients with CRC and 31 age- and sex-matched controls. Tissue VAP-1 levels were measured by immunohistochemistry, quantitative real-time PCR and Western blotting.ResultsThe mean sVAP-1 level ± SD was significantly lower in the CRC group compared with the control group (399 ± 138 ng/ml versus 510 ± 142 ng/ml, P = 0.003). Tissue VAP-1 protein and mRNA levels were significantly lower in CRC compared with normal colon tissue. VAP-1 immunostaining was practically absent from CRC.ConclusionsVAP-1 is downregulated in human CRC and although the molecular basis of this down regulation is not yet known, we suggest it may be part of a mechanism used by the tumour to prevent the recruitment of anti-tumour immune cells. Our data contradicts the findings of others with regard sVAP-1 levels in patients with CRC. Possible reasons for this are discussed.
Highlights
The endothelial adhesion molecule, vascular adhesion protein-1 (VAP-1, amine oxidase (AOC3)) promotes lymphocyte recruitment to tumours, the contribution that VAP-1 makes to lymphocyte recruitment in human colorectal cancer (CRC) is unknown
VAP-1 was originally characterised by a monoclonal antibody that was capable of inhibiting lymphocyte adhesion to high endothelial venules (HEV) and immobilised purified VAP1 protein [6] but it subsequently transpired that the enzymatic activity of VAP-1 is involved in its ability to promote transendothelial migration
Serum soluble VAP-1 (sVAP-1) levels are lower in patients with CRC compared with controls sVAP-1 levels were measured in the serum of 31 patients with proven CRC and 31 age, sex- and ethnic groupmatched control patients who had been investigated for lower gastrointestinal symptoms and proven not to have CRC
Summary
The endothelial adhesion molecule, vascular adhesion protein-1 (VAP-1, AOC3) promotes lymphocyte recruitment to tumours, the contribution that VAP-1 makes to lymphocyte recruitment in human colorectal cancer (CRC) is unknown. Lymphocytes are recruited to tissues from blood via binding to vessels in the target tissue mediated by interactions between specific receptors on the lymphocyte surface and ligands on the endothelium. These interactions involve several families of adhesion molecules including integrins and immunoglobulin superfamily members and selectins. VAP-1 mediates adhesion via heavily sialidated side chains but it functions as a cell surface expressed ectoenzyme—a primary amine oxidase. As such it deaminates primary amines to form the corresponding aldehyde, ammonia and hydrogen peroxide, the physiological substrates are not well defined. VAP-1 was originally characterised by a monoclonal antibody (mAb 1B2) that was capable of inhibiting lymphocyte adhesion to high endothelial venules (HEV) and immobilised purified VAP1 protein [6] but it subsequently transpired that the enzymatic activity of VAP-1 is involved in its ability to promote transendothelial migration
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