Enhanced CMP‐NeuAc:Galβ1, 4GlcNAc‐R α2, 6 sialyltransferase activity of human colon cancer xenografts in athymic nude mice and of xenograft‐derived cell lines

Abstract

The activity of an alpha 2,6 sialyltransferase acting on N-acetyllactosaminic sequences (alpha 2,6 ST E.C. 2.4.99.1) has previously been found to be increased in 90% of human colon cancer specimens. In the present study, the alpha 2,6 ST activity of 6 human colon cancer cell lines grown in culture was compared with that expressed by the corresponding nude mice xenografts and by the cell lines derived from the xenografts. We found that xenografts of COLO 205, HT-29, SW 620, SW 948 and SW 948 FL (a non-adherent sub-line of SW 948) cells express an alpha 2,6 ST activity much higher than that of the in vitro-grown cells. SW 48 cells grown either in culture or as xenografts lack the enzyme activity. All the xenograft-derived cell lines except HT-29 retained the increased alpha 2,6 ST activity at least for the first 6 passages. Those derived from SW 948 xenografts showed an enrichment of round, non-adherent cells, strongly reactive with the NeuAc alpha 2,6 Gal/GalNAc-specific lectin from Sambucus nigra (SNA), thus indicating that a selection of these cells has occurred.

Sialosignaling: Sialyltransferases as engines of self-fueling loops in cancer progression

“…An association between α2,6-sialylation and invasive growth was suggested by early studies [129][130][131]. However, to study the functional implications of the overexpression of ST6GAL1 and/or its cognate Sia6LacNAc structures, we [132] and successively others [133][134][135] obtained stable ST6GAL1 transfectants in different cell lines.…”

Mechanisms of cancer-associated glycosylation changes

“…Owing to the fact that ST6Gal.1 is transcriptionally regulated by the Ras pathway (discussed in section 5.1), it is not clear whether the obvious association of ST6Gal.1 activation with neoplastic transformation merely reflects the activation of the Ras pathway or is causally related to a growth advantage provided by Sia6LacNAc structures. This latter possibility was suggested by the observation that human colon cancer cell lines grown as nude mice xenografts, expressed increased levels of ST6Gal.1 and of Sia6LacNAc than cell lines grown in the usual in vitro conditions (121). To get insights into the causal role of ST6Gal.1 and of the cognate Sia6LacNAc structures in cancer progression, we (122) and others (123)(124)(125) stably inserted the ST6Gal.1 cDNA in different cell types.…”