Correlation Analysis between Tumorous Associated Antigen Sialyl-Tn Expression and ST6GalNAc I Activity in Human Colon Adenocarcinoma

Abstract

Objectives: Sialyl-Tn (sTn) is a mucin carbohydrate-associated antigen that is strongly expressed in a large number of colorectal carcinomas. In this study, we combined immunohistochemical and enzymatic techniques in order to find the correlation between sTn tissue expression and the sialyltransferase activity (ST6GalNAc I) responsible for its synthesis in colorectal cancer (CRC) patients. Methods: We compared sTn expression in healthy (n = 46), tumorous (n = 60) and transitional tissue (n = 46) from CRC patients, and correlated sTn altered expression with clinicopathologic variables of the patient. Furthermore, we determined ST6GalNAc I tissue activity employing asialo-ovine submaxillary mucin (asialo-OSM) as glycoprotein acceptor (n = 27). Results: The rates of sTn positive expression obtained for healthy, tumorous and transitional tissues were 15, 67 and 63%, respectively. These rates led to statistically significant differences between healthy and tumorous or transitional tissue (p = 0.001); sTn expression was related to the first stages of the tumor invasion in transitional tissue. As regards ST6GalNAc I activity, we found an enhancement in transitional tissue. Statistical correlation analysis did not reveal association between sTn expression and ST6GalNAc I activity. Conclusions: Our findings indicated that sTn antigen tissue expression and ST6GalNAc I activity levels were not correlated in CRC, in spite of the overexpression of the antigen in tumorous and transitional tissue.

The ST6GalNAc-I Sialyltransferase Localizes throughout the Golgi and Is Responsible for the Synthesis of the Tumor-associated Sialyl-Tn O-Glycan in Human Breast Cancer

“…Our findings are in contrast to the data relating to the appearance of STn in colon cancers, where no correlation was found between the activity of ␣2,6-sialyltransferase(s) adding sialic acid to GalNAc and STn expression in cancer tissues (32). The explanation for the apparent de novo expression of STn in colon cancer relates to a modification of the sialic acid in the cells of normal colonic tissues.…”

“…One obvious mechanism is an increase in the level of activity of the enzyme(s), which adds sialic acid to GalNAc. Studies in colon carcinoma have demonstrated that this is not the case in this malignancy (32), because the level of ␣2,6-sialyltransferase enzyme activity is similar in normal and cancerous colonic tissue, whereas STn is only detectable in the cancers. The difference in colon carcinoma appears to be due to a lack of detection of the STn on most normal tissue, because of a modification of the sialic acid resulting in it not being recognized by the STn-specific antibodies.…”

Effect of Human Colorectal Carcinogenesis on the Neural Cell Adhesion Molecule Expression and Polysialylation

“…Thus, both PSA and NCAM molecules show a low constitutive expression in control tissue and undergo a statistically significant overexpression in tumor tissue from CRC patients. This type of response is in accordance with those exhibited by other sialylated epitopes in CRC [47,48], but disagrees with previous findings about the presence of NCAM in CRC [34,49]. Roesler et al [34] reported the profile of expression of the 180-kDa NCAM isoform in control and tumor tissue from 15 CRC patients, as well as the association of decreased NCAM expression with poor prognosis.…”

CDX2 homeoprotein is involved in the regulation of ST6GalNAc-I gene in intestinal metaplasia

“…This enzyme, ST6GalNAc-II, was also shown to have some specificity in vitro for GalNAc substrates O-linked to proteins (Tn antigen). Moreover, a lack of concordance observed between ST6GalNAc-I and STn expression in gastric carcinomas has been observed in colorectal carcinomas, 42 and it is known that cell lines and tissues lacking STn may still show low levels of ST6GalNAc-I mRNA, 43 indicating that alternative biosynthetic mechanisms may be at play.…”