Interference with O-glycosylation in RMA lymphoma cells leads to a reduced in vivo growth of the tumor

International Journal of Cancer. Journal International Du Cancer
Liying ChenMikael Jondal

Abstract

Carbohydrate processing in cancer cells can influence the growth, metastatic potential, vascularization and immune recognition of such cells. Interference with N-glycosylation has been shown both to reduce the membrane expression of MHC class I and to increase the in vitro sensitivity of tumor cells to NK cell killing. We investigated the effect of O-glycosylation inhibition on the in vivo growth, phenotype and NK sensitivity of RMA lymphoma cells using benzyl N-acetyl-alpha-D-galactosamide (BAG). BAG-treated cells were found to have a strongly reduced local growth potential in vivo. However, inhibition of O-glycosylation caused this effect without any significant downregulation of MHC-I and increase in sensitivity to NK killing as seen after inhibition of N-glycosylation using Castanospermine. BAG treatment of RMA cells resulted in the removal of larger O-linked glycans and a high expression of the T-antigen (GalGalNAc), a target for natural antibodies (NAs) induced by the gastrointestinal bacterial flora. Whether the loss of larger O-linked glycans, and associated functions, or of biological effects of NA contributed to the antitumor effect remains to be established. The results support the idea that inhibitors of O- as well ...Continue Reading

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Citations

Jan 1, 2013·Vaccines·Behjatolah Monzavi-KarbassiThomas Kieber-Emmons
Nov 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Penelope M DrakeCarolyn R Bertozzi

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