Upregulation of Glycans Containing 3 ' Fucose in a Subset of Pancreatic Cancers Uncovered Using Fusion-Tagged Lectins

• Type of Material: Article
• Authors: Sudhir Singh, Van Andel Research Institute; Kuntal Pal, Van Andel Research Institute; Jessica Yadav, Van Andel Research Institute; Huiyan Tang, Van Andel Research Institute; Katie Partyka, Van Andel Research Institute; Doron Kletter, Palo Alto Research Center; Peter Hsueh, Van Andel Research Institute; Elliot Ensink, Van Andel Research Institute; KC Birendra, Spectrum Health; Galen Hostetter, Van Andel Research Institute; H. Eric Xu, Van Andel Research Institute; Marshall Bern, Palo Alto Research Center; David Smith, Emory University; Anand S. Mehta, Drexel University; Randall Brand, University of Pittsburgh; Karsten Melcher, Van Andel Research Institute; Brian B. Haab, Van Andel Research Institute
• Language: English
• Date: 2015-06-01
• Publisher: American Chemical Society
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 American Chemical Society.
• Final Published Version (URL): http://dx.doi.org/10.1021/acs.jproteome.5b00142
• Title of Journal or Parent Work: Journal of Proteome Research
• ISSN: 1535-3893
• Volume: 14
• Issue: 6
• Start Page: 2594
• End Page: 2605
• Grant/Funding Information: We gratefully acknowledge the Early Detection Research Network (U01CA152653); the Alliance of Glycobiologists for the Detection of Cancer (U01CA168896); and the Van Andel Research Institute for support of this work.; We also thank the supporters of the Purple Community philanthropic foundation for their generous donations.
• Keywords: FUCOSYLATED HAPTOGLOBIN; fucose; PROTEINS; sialyl-Lewis A; Biochemical Research Methods; pancreatic cancer; SERUM; ANTIGEN; Life Sciences & Biomedicine; CA-19-9; antibody-lectin sandwich arrays; LEWIS-X; EXPRESSION; glycan arrays; lectins; ADENOCARCINOMA CELLS; MONOCLONAL-ANTIBODIES; biomarkers; CARBOHYDRATE INTERACTIONS; glycans; Biochemistry & Molecular Biology; Science & Technology
• Research Categories: Chemistry, Biochemistry

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.