Targeted glycoproteomic identification of biomarkers for human breast carcinoma.

Abstract

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.

• Authors: Karen L Abbott, Kazuhiro Aoki, Jae-Min Lim, Mindy Porterfield, Rachelle Johnson, Ruth M O'Regan, Lance Wells, Michael Tiemeyer, Michael Pierce
• Journal: Journal of proteome research (J Proteome Res) Vol. 7 Issue 4 Pg. 1470-80 (Apr 2008) ISSN: 1535-3893 [Print] United States
• PMID: 18271524 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• Cell Adhesion Molecules
• Extracellular Matrix Proteins
• Glycoproteins
• HPR protein, human
• Haptoglobins
• Oligosaccharides, Branched-Chain
• POSTN protein, human
• Phytohemagglutinins

Topics

• Antigens, Neoplasm (analysis)
• Biomarkers, Tumor (analysis)
• Breast Neoplasms (metabolism, pathology)
• Cell Adhesion Molecules (analysis)
• Extracellular Matrix Proteins (analysis)
• Female
• Glycoproteins (analysis, chemistry)
• Haptoglobins (analysis)
• Humans
• Oligosaccharides, Branched-Chain (analysis)
• Phytohemagglutinins (chemistry)
• Proteomics (methods)
• Reproducibility of Results
• Up-Regulation