The O-linked glycosylation of secretory/shed MUC1 from an advanced breast cancer patient's serum.
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.
Storr
Sarah J
SJ
Tumour Immunology Group, University of Nottingham, Division of Breast Surgery, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK. sarah.storr@nottingham.ac.uk
Royle
Louise
L
Chapman
Caroline J
CJ
Hamid
Umi M Abd
UM
Robertson
John F
JF
Murray
Andrea
A
Dwek
Raymond A
RA
Rudd
Pauline M
PM
D001943:Breast Neoplasms / Q000737:chemistry* / Q000378:metabolism; D002236:Carbohydrate Conformation; D002460:Cell Line; D005260:Female; D005936:Glucans / Q000096:biosynthesis / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D018396:Mucin-1 / Q000096:biosynthesis / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000737:chemistry*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry
D005936:Glucans; C060192:MUC1 protein, human; D018396:Mucin-1; D009363:Neoplasm Proteins; D011994:Recombinant Proteins