Identification of the novel differentiation marker MS4A8B and its murine homolog MS4A8A in colonic epithelial cells lost during neoplastic transformation in human colon

The CD20-homolog Ms4a8a has recently been shown to be a marker for alternatively activated macrophages but its expression is not restricted to hematopoietic cells. Here, MS4A8A/MS4A8B expression was detected in differentiated intestinal epithelium in mouse and human, respectively. Interestingly, no...

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Bibliographic Details
Published in:	Cell death & disease Vol. 4; no. 1; p. e469
Main Authors:	Michel, J, Schönhaar, K, Schledzewski, K, Gkaniatsou, C, Sticht, C, Kellert, B, Lasitschka, F, Géraud, C, Goerdt, S, Schmieder, A
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-01-2013 Springer Nature B.V Nature Publishing Group
Subjects:	631/136/142 631/80/82/23 692/53 692/699/67/1504/1885/1393 Animals Antibodies Apoptosis - drug effects Biochemistry Biomedical and Life Sciences Caco-2 Cells Cell Biology Cell Culture Cell Line, Tumor Cell Proliferation Cell Transformation, Neoplastic Colonic Neoplasms - metabolism Colonic Neoplasms - pathology Cytoskeleton Epithelial Cells - metabolism Gene Expression Profiling Humans Hydrogen Peroxide - toxicity Immunology Intestinal Mucosa - pathology Keratin-20 - metabolism Life Sciences Membrane Proteins - genetics Membrane Proteins - metabolism Mice Mice, Inbred BALB C Original original-article Reactive Oxygen Species - metabolism colon carcinoma apoptosis proliferation Differentiation of enterocytes keratin 20
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Summary:	The CD20-homolog Ms4a8a has recently been shown to be a marker for alternatively activated macrophages but its expression is not restricted to hematopoietic cells. Here, MS4A8A/MS4A8B expression was detected in differentiated intestinal epithelium in mouse and human, respectively. Interestingly, no MS4A8B expression was found in human colon carcinoma. Forced overexpression of MS4A8A in the murine colon carcinoma cell line CT26 led to a reduced proliferation and migration rate. In addition, MS4A8A-expressing CT26 cells displayed an increased resistance to hydrogen peroxide-induced apoptosis, which translated in an increased end weight of subcutaneous MS4A8A+ CT26 tumors. Gene profiling of MS4A8A+ CT26 cells revealed a significant regulation of 225 genes, most of them involved in cytoskeletal organization, apoptosis, proliferation, transcriptional regulation and metabolic processes. Thereby, the highest upregulated gene was the intestinal differentiation marker cytokeratin 20. In conclusion, we show that MS4A8A/MS4A8B is a novel differentiation marker of the intestinal epithelium that supports the maintenance of a physiological barrier function in the gut by modulating the transcriptome and by conferring an increased resistance to reactive oxygen species. The absence of MS4A8B in human colonic adenocarcinomas shown in this study might be a helpful tool to differentiate between healthy and neoplastic tissue.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	2041-4889 2041-4889
DOI:	10.1038/cddis.2012.215