Role of sialyltransferases involved in the biosynthesis of Lewis antigens in human pancreatic tumour cells

Abstract

The sialylated carbohydrate antigens, sialyl-Lewisx and sialyl-Lewisa, are expressed in pancreatic tumour cells and are related to their metastatic potential. While the action of the fucosyltransferases involved in the synthesis of these antigens has already been investigated, no studies have been carried out on the activity and expression of the alpha 2,3-sialyltransferases in pancreatic tumour cells. We describe the sialyltransferase (ST) activity, mRNA expression, and analysis of the cell carbohydrate structures in four human pancreatic adenocarcinoma cell lines of a wide range of neoplastic differentiation stages and in normal human pancreatic tissues. Total ST activity measured on asialofetuin, employing a CMP fluorescent sialic acid, varied among the pancreatic cell lines and could be correlated to the expression of their cell surface antigens. However, in some of the pancreatic cell lines, no relationship could be established with their ST3Gal III and IV mRNA expression. Human pancreatic tissues also showed ST expression and activity. However, it presented a much higher expression of neutral fucosylated structures than sialylated structures. In conclusion, ST activity levels in pancreatic cells could be correlated to their expression of sialylated epitopes, which indicates their involvement in the formation of the sialyl-Lewis antigens, in addition to fucosyltransferase activities.

Antimetastatic therapy targeting aberrant sialylation profiles in cancer cells

“…Now, many sialyltransferases or sialidases have been found to be expressed relatively higher or lower in tumors than in normal tissues. [19][20][21][22] Cancer stem cells or cancer stem-like cells that are especially important with resistance to chemotherapy, radiation and neoplasm metastasis are important models for pathologic and therapeutic study of sias in tumors. Since sialyltransferases and sialidases appear to have important functions in normal stem cells as well as in development.…”

Adhesion molecules and chemokines: the navigation system for circulating tumor (stem) cells to metastasize in an organ-specific manner

“…Both, sLe a and sLe x are typical tumor associated carbohydrate antigens and have been implicated with tumor progression and enhanced metastasis formation [40] of different neoplasias including colon and colorectal cancer [41][42][43][44][45][46][47], lung cancer [48][49][50][51], gastric cancer [52,53], pancreatic cancer [54,55], prostate cancer [56,57], and breast cancer [58]. Sialyl Lewis a is a prognostic factor in colon and colorectal cancer whereby increased sLe a levels are associated with a poor prognosis of the afflicted patients [41,42,45].…”

Mucin impedes cytotoxic effect of 5-FU against growth of human pancreatic cancer cells: overcoming cellular barriers for therapeutic gain

“…In several pancreatic cancer cells the presence of terminal sialic acid sugar moiety on carbohydrate chains is higher due to the overexpression of sialyltransferases (Peracaula et al, 2005). We next determined whether the removal of the terminal sialic acid moiety of underglycosylated mucin sufficient to improve cytotoxic action of 5-FU, or is removal of the entire carbohydrate chain required.…”

“…Analysis of normal and tumour-derived mucins revealed that the carbohydrate chains of mucins are shorter and more sialyated in developing tumours compared to normal tissues (Beum et al, 1999;Peracaula et al, 2005). The synthesis of mucin on the surface of normal epithelial cells is under strict regulation, but in tumours there is an overabundance of mucin mainly due to elevated expression of MUC1.…”