Tumor-related expression of  1,2fucosylated antigens on colorectal carcinoma cells and its suppression by cell-mediated priming using sugar acceptors for  1,2fucosyltransferase

Abstract

The accumulation of alpha1,2fucosylated antigens, such as Y (Fucalpha1,2Galbeta1,4 [Fucalpha1,3]GlcNAcbeta), Le(b) (Fucalpha1,2Galbeta1,3-[Fucalpha1,4]GlcNAcbeta), and H type 2 (Fucalpha1,2 Galbeta1,4GlcNAcbeta) occurs specifically within human colorectal tumor tissues and can be detected by an antifucosylated antigen antibody, such as the YB-2 antibody. In the present investigation, we found that the expression of these antigens bearing an alpha1,2-linked fucose correlated with the resistance of the tumor cells to anticancer treatments. Addition of an exogenous sugar acceptor for alpha1,2fucosyltransferase to the cell medium resulted in suppression of alpha1,2fucosylated antigen expression on the tumor cells and increased susceptibility to anticancer treatment. The increased susceptibility may be attributed to cancer cell-mediated priming by sugar acceptors for alpha1,2fucosyltransferase added to the medium.

Introducing α(1,2)‐linked fucose into hepatocarcinoma cells inhibits vasculogenesis and tumor growth

“…34 Other studies showed that blocking a(1,2)-fucosylation increased cell sensitivity to anticancer drugs. 43 Interestingly, we have previously shown that FUT1 affected E-selectin-mediated adhesion in some cell lines, including HepG2 cells (see also the present study) and the colon carcinoma cells HT29, but had no effect on other cells, such as pancreatic cancer cells BxPC3, 11 suggesting that the effect of FUT1 is cell-dependent.…”

Novel sugar-cholestanols as anticancer agents against peritoneal dissemination of tumor cells

“…In contrast, cell-mediated priming by certain glycoconjugates in colorectal cancer cells showed that novel antitumor agents might exist among such glycoconjugates [5]. However, it is plausible that treatment of cancer cells with the present sugar-cholestanols achieves more potent advantages as an anticancer agent.…”

“…Furthermore, the amounts of tumor-associated antigens including α1-2fucosylated antigens and the SLX antigen expressed on the cancer cell surface, could be selectively suppressed, and this enhanced the susceptibility of cancer cells to anticancer treatments [5]. More recently, the same primers were shown to have strong inhibiting actions on the proliferation of cancer cells when the concentrations of the primers were increased [17,18].…”

“…Tumor cells aberrantly express various glycoconjugates on their surface to control different aspects of tumor behavior, such as proliferation, invasion, angiogenesis and metastasis [1][2][3][4][5][6]. Accordingly, the properties of aberrant glycoconjugates should guide the design of therapeutic interventions for the treatment of malignancy.…”

“…Based on this understanding, we recently developed anti-adhesion molecules consisting of chemically synthesized sugars against the peritoneal dissemination of cancer cells [12][13][14]. Likewise, using chemically synthesized oligosaccharides consisting of sugar moieties attached to hydrophobic aglycones, we found that cancer cells could utilize such oligosaccharides as substrates for cellular fucosyltransferases and this resulted in the suppression of tumor-specific fucosylated antigen expression along with cell-mediated priming of the oligosaccharides and an increase in the susceptibility of cancer cells to anticancer agents [5]. The same priming effect of chemically synthesized disaccharide attached to naphthalenemethanol was also reported on the suppression of the formation of the sialyl Le X (SLX) antigen in cancer cells leading to the inhibition of selectin-mediated cell adhesion and their metastatic potential [15,16].…”