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

Int J Cancer. 2006 Sep 15;119(6):1495-500. doi: 10.1002/ijc.21981.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylgalactosamine / analogs & derivatives
  • Acetylgalactosamine / metabolism
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Benzyl Compounds / metabolism
  • Cell Survival
  • Enzyme Inhibitors / pharmacology*
  • Glucosylceramidase / antagonists & inhibitors*
  • Glycosylation
  • Humans
  • Indolizines / pharmacology*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / metabolism
  • Lymphoma / metabolism
  • Lymphoma / pathology*
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Tumor Cells, Cultured


  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzyl Compounds
  • Enzyme Inhibitors
  • Indolizines
  • benzyl-alpha-N-acetylgalactosamine
  • Glucosylceramidase
  • Acetylgalactosamine
  • castanospermine