Anti-ANXA1 monoclonal antibody, clone 6F5/2

Background: Annexin A1 (ANXA1) is known to be involved in the progression and differentiation of various tumors. However, its significance and role in bladder carcinogenesis has not been fully elucidated. To determine the role ANXA1 plays in urothelial carcinoma (UC), we investigated the expression of ANXA1 protein in normal urothelial tissue, carcinoma in situ (CIS), and UC of the urinary bladder. Methods: Protein expression level of ANXA1 and its subcellular localization were analyzed in 88 cases of UCs and corresponding 24 normal tissues and 24 CISs by immunohistochemistry. Results: ANXA1 was significantly down-regulated at all subcellular localization in CIS and in the cytoplasm and membrane of cells of UC, compared to normal tissues. No significant correlation between ANXA1 expression level and tumor depth (pT), growth pattern, and recurrence was found. However, cytoplasmic and membranous ANXA1 were significantly up-regulated in high grade than in low grade UC (p=0.02 in cytoplasm and p=0.03 in membrane). Conclusions: These results suggest that ANXA1 dysregulation is involved in urothelial carcinogenesis and ANXA1 is potentially a marker for the pathologic differentiation of UC.

Immunosuppressive drugs have a critical role in inhibiting tissue damage and allograft rejection. Studies have demonstrated the anti-inflammatory effects of the annexin A1 (AnxA1) in the regulation of transmigration and apoptosis of leucocytes. In the present study, an experimental skin allograft model was used to evaluate a potential protective effect of AnxA1 in transplantation survival. Mice were used for the skin allograft model and pharmacological treatments were carried out using either the AnxA1 mimetic peptide Ac2-26, with or without cyclosporine A (CsA), starting 3days before surgery until rejection. Graft survival, skin histopathology, leucocyte transmigration and expression of AnxA1 and AnxA5 post-transplantation were analysed. Pharmacological treatment with Ac2-26 increased skin allograft survival related with inhibition of neutrophil transmigration and induction of apoptosis, thereby reducing the tissue damage compared with control animals. Moreover, AnxA1 and AnxA5 expression increased after Ac2-26 treatment in neutrophils. Interestingly, the combination of Ac2-26 and cyclosporine A showed similar survival of transplants when compared with the cyclosporine A group, which could be attributed to a synergistic effect of both drugs. Investigations in vitro revealed that cyclosporine A inhibited extracellular-signal-regulated kinase (ERK) phosphorylation induced by Ac2-26 in neutrophils. Overall, the results suggest that AnxA1 has an essential role in augmenting the survival of skin allograft, mainly owing to inhibition of neutrophil transmigration and enhancement of apoptosis. This effect may lead to the development of new therapeutic approaches relevant to transplant rejection. Copyright (c) 2013 John Wiley & Sons, Ltd.