Interference with O-glycosylation in RMA lymphoma cells leads to a reduced in vivo growth of the tumor.
Int J Cancer
; 119(6): 1495-500, 2006 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-16615117
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 as N-linked glycosylation may be useful for the treatment of cancer, given that they can be specifically targeted to the tumor tissue.
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Base de dados:
MEDLINE
Assunto principal:
Inibidores Enzimáticos
/
Glucosilceramidase
/
Indolizinas
/
Linfoma
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article