Differential expression of Cosmc, T-synthase and mucins in Tn-positive colorectal cancers

• Type of Material: Article
• Authors: Xiaodong Sun, Beth Israel Deaconess Medical Center; Tongzhong Ju, Emory University; Richard D. Cummings, Beth Israel Deaconess Medical Center
• Language: English
• Date: 2018-08-16
• Publisher: BMC (part of Springer Nature)
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12885-018-4708-8
• Title of Journal or Parent Work: BMC Cancer
• ISSN: 1471-2407
• Volume: 18
• Issue: 1
• Start Page: 827
• End Page: 827
• Grant/Funding Information: The funding body was not directly involved in the design of the study or collection, analysis, and interpretation of data or in writing the manuscript.; This work was supported by National Institutes of Health Grant U01CA168930 to T.J. and R.D.C.
• Keywords: Colorectal carcinoma; HEPATOCELLULAR-CARCINOMA; Tn antigen; CHAPERONE COSMC; CELL-LINES; Cosmc; ANTIGEN-EXPRESSION; T-synthase; Life Sciences & Biomedicine; BINDING-PROTEINS; COMPLEX-FORMATION; STn antigen; HUMAN-COLON-CANCER; Science & Technology; SIALOSYL-TN; Oncology; GLYCANS; Mutation; O-GLYCOSYLATION
• Research Categories: Health Sciences, Oncology; Chemistry, Biochemistry

Abstract

Background: The Tn neoantigen (GalNAcα1-O-Ser/Thr) is an O-glycan expressed in various types of human cancers. Studies in several Tn-expressing cancer cell lines and pancreatic tumors have identified loss of Cosmc expression caused by either mutations or promoter hypermethylation. In this study, we explored the mechanism(s) for Tn expression in human colorectal cancers (CRC). Methods: Tn-expressing cell populations were isolated from CRC cell lines by Fluorescence-associated cell sorting (FACS). The expression of the Tn and sialylated Tn (STn) antigens, Cosmc, T-synthase, and mucins was characterized in paired specimens with CRC and in CRC cell lines by immunostaining, western blot, and qPCR. Results: Using well-defined monoclonal antibodies, we confirmed prevalent Tn/STn expression in CRC samples. However, a majority of these tumors had elevated T-synthase activity and expression of both Cosmc and T-synthase proteins. Meanwhile, Tn antigen expression was not caused by mucin overproduction. In addition, we found that Tn-expressing CRC cell lines had either loss-of-function mutations in Cosmc or reversible Tn antigen expression, which was not caused by the deficiency of T-synthase activity. Conclusions: Our results demonstrate multiple mechanisms for Tn expression in CRCs.