Targeted glycoproteomic identification of biomarkers for human breast carcinoma.

Abbott KL, Aoki K, Lim JM, Porterfield M, Johnson R, O'Regan RM, Wells L, Tiemeyer M, Pierce M
J Proteome Res. 2008 7 (4): 1470-80

PMID: 18271524 · PMCID: PMC4932838 · DOI:10.1021/pr700792g

Glycosylation is a dynamic post-translational modification that changes during the development and progression of various malignancies. During the oncogenesis of breast carcinoma, the glycosyltransferase known as N-acetylglucosaminyltransferase Va (GnT-Va) transcript levels and activity are increased due to activated oncogenic signaling pathways. Elevated GnT-V levels leads to increased beta(1,6)-branched N-linked glycan structures on glycoproteins that can be measured using a specific carbohydrate binding protein or lectin known as L-PHA. L-PHA does not bind to nondiseased breast epithelial cells, but during the progression to invasive carcinoma, cells show a progressive increase in L-PHA binding. We have developed a procedure for intact protein L-PHA-affinity enrichment, followed by nanospray ionization mass spectrometry (NSI-MS/MS), to identify potential biomarkers for breast carcinoma. We identified L-PHA reactive glycoproteins from matched normal (nondiseased) and malignant tissue isolated from patients with invasive ductal breast carcinoma. Comparison analysis of the data identified 34 proteins that were enriched by L-PHA fractionation in tumor relative to normal tissue for at least 2 cases of ductal invasive breast carcinoma. Of these 34 L-PHA tumor enriched proteins, 12 are common to all 4 matched cases analyzed. These results indicate that lectin enrichment strategies targeting a particular glycan change associated with malignancy can be an effective method of identifying potential biomarkers for breast carcinoma.

MeSH Terms (14)

Antigens, Neoplasm Biomarkers, Tumor Breast Neoplasms Cell Adhesion Molecules Extracellular Matrix Proteins Female Glycoproteins Haptoglobins Humans Oligosaccharides, Branched-Chain Phytohemagglutinins Proteomics Reproducibility of Results Up-Regulation

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