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‐α‐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 as N‐linked glycosylation may be useful for the treatment of cancer, given that they can be specifically targeted to the tumor tissue. © 2006 Wiley‐Liss, Inc.