Use of model cell lines to study the biosynthesis and biological role of cancer-associated sialosyl-Tn antigen

Abstract

Sialosyl-Tn (STn) is a mucin-associated carbohydrate antigen that is not expressed by most normal epithelial cells but becomes expressed in several types of adenocarcinomas, where it is often associated with a poor prognosis. Little is known about the regulation of the STn phenotype in tumor cells and the immune response to STn antigen. In the present study, we established clonal cell lines in which virtually all of the cells were STn positive (designated LS-C) or STn negative (designated LS-B). These two cell lines, derived from a single parental cell line, LS174T, have the same total protein electrophoretic profiles but carry markedly different oligosaccharide structures on their mucin; the mucin from LS-C cells has only the Tn and STn structures, whereas LS-B cell mucin lacks these simple structures but carries more complex oligosaccharides. These results indicate that lack of STn expression by cells can be due to the lack of STn synthesis rather than inaccessibility of antibodies to bind to STn by steric hindrance. Both clones were similar in their growth rates, response to gamma-interferon, and sensitivity to lysis by lymphokine-activated killer cells. These cells may be important models for understanding the regulation of glycosylation at the cellular level and for further studies of tumor biology and immune response to STn antigen.