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

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, Galbeta1-3GalNAc) 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.

• Authors: Arne Engelsberg, Ricardo Hermosilla, Uwe Karsten, Ralf Schülein, Bernd Dörken, Armin Rehm
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 278 Issue 25 Pg. 22998-3007 (Jun 20 2003) ISSN: 0021-9258 [Print] United States
• PMID: 12672804 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• DNA Primers
• EBAG9 protein, human
• Polysaccharides
• Recombinant Proteins

Topics

• Antigens, Neoplasm (metabolism)
• Base Sequence
• Biotinylation
• Breast Neoplasms
• Cell Line
• DNA Primers
• Female
• Glycosylation
• Golgi Apparatus (metabolism)
• Humans
• Kidney
• Polymerase Chain Reaction
• Polysaccharides (metabolism)
• Recombinant Proteins (metabolism)
• Transfection
• Tumor Cells, Cultured
• Urothelium