Upregulation of glycans containing 3' fucose in a subset of pancreatic cancers uncovered using fusion-tagged lectins.

Abstract

The fucose post-translational modification is frequently increased in pancreatic cancer, thus forming the basis for promising biomarkers, but a subset of pancreatic cancer patients does not elevate the known fucose-containing biomarkers. We hypothesized that such patients elevate glycan motifs with fucose in linkages and contexts different from the known fucose-containing biomarkers. We used a database of glycan array data to identify the lectins CCL2 to detect glycan motifs with fucose in a 3' linkage; CGL2 for motifs with fucose in a 2' linkage; and RSL for fucose in all linkages. We used several practical methods to test the lectins and determine the optimal mode of detection, and we then tested whether the lectins detected glycans in pancreatic cancer patients who did not elevate the sialyl-Lewis A glycan, which is upregulated in ∼75% of pancreatic adenocarcinomas. Patients who did not upregulate sialyl-Lewis A, which contains fucose in a 4' linkage, tended to upregulate fucose in a 3' linkage, as detected by CCL2, but they did not upregulate total fucose or fucose in a 2' linkage. CCL2 binding was high in cancerous epithelia from pancreatic tumors, including areas negative for sialyl-Lewis A and a related motif containing 3' fucose, sialyl-Lewis X. Thus, glycans containing 3' fucose may complement sialyl-Lewis A to contribute to improved detection of pancreatic cancer. Furthermore, the use of panels of recombinant lectins may uncover details about glycosylation that could be important for characterizing and detecting cancer.

• Authors: Sudhir Singh, Kuntal Pal, Jessica Yadav, Huiyuan Tang, Katie Partyka, Doron Kletter, Peter Hsueh, Elliot Ensink, Birendra Kc, Galen Hostetter, H Eric Xu, Marshall Bern, David F Smith, Anand S Mehta, Randall Brand, Karsten Melcher, Brian B Haab
• Journal: Journal of proteome research (J Proteome Res) Vol. 14 Issue 6 Pg. 2594-605 (Jun 05 2015) ISSN: 1535-3907 [Electronic] United States
• PMID: 25938165 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CCL2 protein, human
• Chemokine CCL2
• Lectins
• Molecular Probes
• Polysaccharides
• Fucose

Topics

• Adenocarcinoma (metabolism)
• Chemokine CCL2 (metabolism)
• Fucose (metabolism)
• Humans
• Lectins (metabolism)
• Molecular Probes
• Pancreatic Neoplasms (metabolism)
• Polysaccharides (chemistry, metabolism)
• Up-Regulation