Upregulation of glycans containing 3' fucose in a subset of pancreatic cancers uncovered using fusion-tagged lectins.
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.
†Van Andel Research Institute, Grand Rapids, Michigan 49503, United States.
Sudhir
S
Singh
†Van Andel Research Institute, Grand Rapids, Michigan 49503, United States.
Kuntal
K
Pal
†Van Andel Research Institute, Grand Rapids, Michigan 49503, United States.
Jessica
J
Yadav
†Van Andel Research Institute, Grand Rapids, Michigan 49503, United States.
Huiyuan
H
Tang
†Van Andel Research Institute, Grand Rapids, Michigan 49503, United States.
Katie
K
Partyka
‡Palo Alto Research Center, Palo Alto, California 94304, United States.
Doron
D
Kletter
†Van Andel Research Institute, Grand Rapids, Michigan 49503, United States.
Peter
P
Hsueh
†Van Andel Research Institute, Grand Rapids, Michigan 49503, United States.
Elliot
E
Ensink
§Spectrum Health, Grand Rapids, Michigan 49503, United States.
Birendra
B
Kc
†Van Andel Research Institute, Grand Rapids, Michigan 49503, United States.
Galen
G
Hostetter
†Van Andel Research Institute, Grand Rapids, Michigan 49503, United States.
H Eric
HE
Xu
‡Palo Alto Research Center, Palo Alto, California 94304, United States.
Marshall
M
Bern
∥Emory University, Atlanta, Georgia 30322, United States.
David F
DF
Smith
⊥Drexel University, Philadelphia, Pennsylvania 19104, United States.
Anand S
AS
Mehta
#University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, United States.
Randall
R
Brand
†Van Andel Research Institute, Grand Rapids, Michigan 49503, United States.
Karsten
K
Melcher
†Van Andel Research Institute, Grand Rapids, Michigan 49503, United States.
Brian B
BB
Haab
D000230:Adenocarcinoma / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D005643:Fucose / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D015335:Molecular Probes; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D015854:Up-Regulation
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D037102:Lectins; D015335:Molecular Probes; D011134:Polysaccharides; D005643:Fucose
antibody-lectin sandwich arrays; biomarkers; fucose; glycan arrays; glycans; lectins; pancreatic cancer; sialyl-Lewis A