Research Highlights

Tumor glycosylation: Sialic acid self-protection

Ribbon model of galectin-3. Copyright © Consortium for Functional Glycomics.

Cancer-cell-related alterations of surface glycans and glycan-binding proteins have been shown to promote cancer development. Notably, some cancer cells upregulate both the ST6Gal-I sialyltransferase and galectin-3 (gal-3). ST6Gal-I extends N-glycans by adding 2,6-linked sialic acid to lactosamines, whereas extracellular gal-3 binds to galactosides on transmembrane proteins such as integrins. Research by Zhuo et al. published in the Journal of Biological Chemistry shows that both events may be interrelated in an intriguing way.

The authors observed a reduced adhesion of SW48 colon cancer cells transfected with ST6Gal-1 (ST6 cells) to a gal-3 matrix, which reverted to the level of SW48 cells upon treatment with sialidase. SW48 adhesion was established by 1 integrins as the incubation of SW48 cells with a 1 integrin-specific antibody blocked adhesion to the gal-3 matrix. Finally, using a blot overlay the authors showed that gal-3 binds directly to 1 integrins from SW48 cells, but not from ST6 cells, indicating that sialylation blocks gal-3 binding to 1 integrin lactosamines.

Gal-3 binding is known to induce apoptosis. However, the authors noted that neither ST6 nor SW48 cells treated with an antibody against 1 integrins underwent apoptosis after treatment with gal-3. Furthermore, apoptosis was also absent when Zhuo et al. incubated SW48 cells both with gal-3 and lactose, which binds to the galectin. These findings indicate that the gal-3 binding to the N-glycans on 1 integrins elicits apoptosis.

The authors point out that intracellular — as opposed to secreted — gal-3 is known to shield the cell from apoptosis. Secreted gal-3, in turn, has been shown to support tumor angiogenesis and to induce T-cell apoptosis, which attenuates anti-tumor immune responses. Thus, cancer cells may increase lactosamine sialylation to benefit from secreted gal-3 without being exposed to its destructive effects. Increased sialylation is known to protect cancer cells against attacks from the immune system — this study shows another aspect in which way it serves self-protection.

Author: Mirko von Elstermann