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Reevaluation of the 22-1-1 antibody and its putative antigen, EBAG9/RCAS1, as a tumor marker

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Item Type:Article
Title:Reevaluation of the 22-1-1 antibody and its putative antigen, EBAG9/RCAS1, as a tumor marker
Creators Name:Reimer, T.A. and Anagnostopoulos, I. and Erdmann, B. and Lehmann, I. and Stein, H. and Daniel, P. and Doerken, B. and Rehm, A.
Abstract:BACKGROUND: Tumor-associated antigens are appreciated as diagnostic markers, but they have also prompted tremendous efforts to develop tumor-specific immunotherapy. A previously cloned tumor-associated antigen, EBAG9, was initially defined by reactivity with the monoclonal antibody 22-1-1. Functionally, the EBAG9-encoded gene-product was believed to induce apoptosis in activated immune cells. However, using a cell-biological approach we identified EBAG9 as a Golgi-resident modulator of O-linked glycan expression, the latter product was then recognized by the 22-1-1 antibody. Secondly, EBAG9 expression was found physiologically in all murine tissues examined. This raised the question if EBAG9 is tumor-specific and mediates apoptosis itself or through O-linked glycans generated, among them the cognate 22-1-1 antigen Tn. METHODS: We have used immunohistochemistry to detect the expression of 22-1-1 and EBAG9 in various tissues. Correlation between expression of both antigens in cell lines was analysed by immunoblot and flow cytometry. Apoptosis was studied by using flow cytometry and Caspase-Glo 3/7 assay kit. Cellular distribution of EBAG9 was analysed by electron and confocal microscopy. RESULTS: Here, we compared expression of the 22-1-1 and EBAG9-defined antigens in normal and neoplastic tissues in situ. In contrast to 22-1-1 staining, EBAG9 is a ubiquitously expressed antigen in all normal and cancerous tissues. Functional studies on the role of 22-1-1 reactive material did not support any evidence for apoptosis induction. Employing electron and confocal microscopy, a refined subcellular localization of EBAG9 at the Golgi was obtained. CONCLUSION: We suggest that the estrogen-inducible EBAG9 gene-product and the 22-1-1 defined antigen are structurally and functionally separate antigens.
Keywords:Adenocarcinoma, Monoclonal Antibodies, Neoplasm Antigens, Carbohydrate Tumor-Associated Antigens, Antineoplastic Agents, Apoptosis, Brefeldin A, Squamous Cell Carcinoma, Caspases, Tumor Cell Line, Cell Nucleus, Colorectal Neoplasms, Flow Cytometry, Golgi Apparatus, Immunoblotting, Immunohistochemistry, Immunotherapy, Lung Neoplasms, Confocal Microscopy, Electron Microscopy, Mouth Neoplasms, Nocodazole, Polysaccharides, Prostatic Neoplasms, Protein Synthesis Inhibitors, Reverse Transcriptase Polymerase Chain Reaction, Stomach Neoplasms, Subcellular Fractions, Tissue Distribution, Biological Tumor Markers
Source:BMC Cancer
ISSN:1471-2407
Publisher:BioMed Central (U.K.)
Volume:5
Number:1
Page Range:47
Date:1 January 2005
Official Publication:https://doi.org/10.1186/1471-2407-5-47
PubMed:View item in PubMed

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