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.