N-glycomic changes in human breast carcinoma MCF-7 and T-lymphoblastoid cells after treatment with herceptin and herceptin/Lipoplex.
The humanized monoclonal antibody IgG1 in combination with chemotherapy has been demonstrated to enhance survival benefit in cancer treatment. Despite positive outcomes, some cancer cells develop multidrug resistance. Numerous mechanisms in cancers can be involved in the process of treatment therapy and most of them are not still well understood. To address how the carbohydrate moieties of cells are affected during treatment, the glycan profiles from the two most common cancer cell lines - human breast MCF-7 carcinoma and T-lymphoblastoid CEM cells - were studied here and compared with profiles after treatment with Herceptin alone or in combination with Lipofectamine mixed with plasmid DNA to form Lipoplex. N-Glycans were released from total cells by digestion with PNGaseF and analyzed by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). In summary, both original cell lines showed a dominant occurrence of high-mannose glycans. After treatment, these structures were suppressed and biantennary core-fucosylated glycans originating from IgG1 were the major carbohydrate products identified in cells. The high incidence of additional fucosylated or nonfucosylated galactosylated oligosaccharides, which were not detected in original cells or Herceptin, varied with conditions and time of exposure of cells to the antibody. The results presented in this study provide strong evidence for a role of glycosylation during antibody treatment.
Lattová
Erika
E
Department of Chemistry, University of Manitoba, 144 Dysart Road, Winnipeg, Manitoba R3T 2N2, Canada.
Tomanek
Boguslaw
B
Bartusik
Dorota
D
Perreault
Hélène
H
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000378:metabolism* / Q000628:therapy*; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage; D005260:Female; D054794:Glycomics / Q000379:methods; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000494:pharmacology*; D013058:Mass Spectrometry; D010957:Plasmids / Q000008:administration & dosage; D011134:Polysaccharides / Q000378:metabolism*; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008055:Lipids; C086724:Lipofectamine; D011134:Polysaccharides; D004247:DNA; D000068878:Trastuzumab