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 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.
Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
J
J
Michel
K
K
Schönhaar
K
K
Schledzewski
C
C
Gkaniatsou
C
C
Sticht
B
B
Kellert
F
F
Lasitschka
C
C
Géraud
S
S
Goerdt
A
A
Schmieder
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton; D004847:Epithelial Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007413:Intestinal Mucosa / Q000473:pathology; D053554:Keratin-20 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D017382:Reactive Oxygen Species / Q000378:metabolism
D053554:Keratin-20; C438731:MS4A7 protein, human; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide