The O-linked glycosylation of secretory/shed MUC1 from an advanced breast cancer patient's serum

Glycobiology. 2008 Jun;18(6):456-62. doi: 10.1093/glycob/cwn022. Epub 2008 Mar 10.

Abstract

MUC1 is a high molecular weight glycoprotein that is overexpressed in breast cancer. Aberrant O-linked glycosylation of MUC1 in cancer has been implicated in disease progression. We investigated the O-linked glycosylation of MUC1 purified from the serum of an advanced breast cancer patient. O-Glycans were released by hydrazinolysis and analyzed by liquid chromatography-electrospray ionization-mass spectrometry and by high performance liquid chromatography coupled with sequential exoglycosidase digestions. Core 1 type glycans (83%) dominated the profile which also confirmed high levels of sialylation: 80% of the glycans were mono-, di- or trisialylated. Core 2 type structures contributed approximately 17% of the assigned glycans and the oncofoetal Thomsen-Friedenreich (TF) antigen (Galbeta1-3GalNAc) accounted for 14% of the total glycans. Interestingly, two core 1 type glycans were identified that had sialic acid alpha2-8 linked to sialylated core 1 type structures (9% of the total glycan pool). This is the first O-glycan analysis of MUC1 from the serum of a breast cancer patient; the results suggest that amongst the cell lines commonly used to express recombinant MUC1 the T47D cell line processes glycans that are most similar to patient-derived material.

MeSH terms

  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / metabolism
  • Carbohydrate Conformation
  • Cell Line
  • Female
  • Glucans / biosynthesis
  • Glucans / chemistry*
  • Glycosylation
  • Humans
  • Mucin-1 / biosynthesis
  • Mucin-1 / chemistry*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / chemistry*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry

Substances

  • Glucans
  • MUC1 protein, human
  • Mucin-1
  • Neoplasm Proteins
  • Recombinant Proteins