The Golgi protein RCAS1 controls cell surface expression of tumor-associated O-linked glycan antigens

Item Type:	Article
Title:	The Golgi protein RCAS1 controls cell surface expression of tumor-associated O-linked glycan antigens
Creators Name:	Engelsberg, A. and Hermosilla, R. and Karsten, U. and Schuelein, R. and Doerken, B. and Rehm, A.
Abstract:	Tumor immunology has received a large impetus from the identification of tumor-associated antigens. Among them, a monoclonal antibody, 22.1.1, was instrumental in defining a novel tumor-associated antigen that was termed "receptor binding cancer antigen expressed on SiSo cells" (RCAS1). RCAS1 was proposed to induce growth arrest and apoptosis on activated immune cells, mediated by a putative death receptor. Structurally, RCAS1 was predicted to exist as a type II transmembrane protein and in a soluble form. Here, we analyzed occurrence, membrane topology, and subcellular localization of the RCAS1-encoded gene product. RCAS1 was shown to be a ubiquitously expressed type III transmembrane protein with a Golgi-predominant localization. Monoclonal antibody 22.1.1 failed to recognize RCAS1, as demonstrated by confocal microscopy. Instead, we showed that the cognate 22.1.1 epitope is identical with the tumor-associated O-linked glycan Tn (N-acetyl-D-galactosamine, GalNAc). Overexpression of RCAS1 in cell lines that are negative for 22.1.1 surface staining led to the generation of Tn and the closely related TF (Thomsen-Friedenreich, Gal{beta}1-3GalNAc) antigen, thus providing a functional link to the generation of the 22.1.1 epitope. We suggest that RCAS1 modulates surface expression of tumor-associated, normally cryptic O-linked glycan structures and contributes indirectly to the antigenicity of tumor cells.
Keywords:	Base Sequence, Biotinylation, Breast Neoplasms, Cell Line, COMT Genotype, Cultured Tumor Cells, DNA Primers, Dopamine, Glycosylation, Golgi Apparatus, Kidney, Neoplasm Antigens, P300, Prefrontal Noise, Polymerase Chain Reaction, Polysaccharides, Recombinant Proteins, Transfection, Urothelium
Source:	Journal of Biological Chemistry
ISSN:	0021-9258
Publisher:	American Society for Biochemistry and Molecular Biology
Volume:	278
Number:	25
Page Range:	22998-23007
Date:	1 January 2003
Official Publication:	https://doi.org/10.1074/jbc.M301361200
PubMed:	View item in PubMed

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