Expression of the high-affinity selectin glycan ligand C2-O-sLe X by colon carcinoma cells

Catherine A.St Hill, Kelli M. Bullard, Bruce Walcheck

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22 Scopus citations

Abstract

The selectin family of adhesion proteins directs leukocytes in the blood to lymphoid organs and sites of inflammation, and is also thought to be involved in the dissemination of carcinomas expressing sialylated Lewis glycan structures, such as sialyl-Lewis X (sLe X). The expression of core 2 β1,6 N-acetylglucosaminyltransferase (C2GnT) by leukocytes allows for the biosynthesis of core 2 O-glycans that when terminated by sLe X can serve as high-affinity selectin glycan ligands. In particular, the sLe X-modified core 2 O-glycan structure C2-O-sLe X has been directly demonstrated to confer significantly higher affinity selectin binding than sLe X. We have recently described the reactivity of the mAb CHO-131, which is dependent on the enzymes α2,3-sialyltransferase, α1,3-fucosyltransferase, and C2GnT, and specifically recognizes the glycan structure C2-O-sLe X. Here we examined a defined pair of colon carcinoma cell lines that are distinct in their capacity to bind E-selectin, as demonstrated by shear flow assays involving whole blood and shear stresses that occur in the microvasculature. CHO-131 demonstrated reactivity with such cancer cells, but only with the cell line that avidly attached to E-selectin. Hence, we demonstrate for the first time the detection of C2-O-sLe X on colon carcinoma cells, which, as with leukocytes, may be directly relevant to the expression of high affinity glycan ligands for the selectins.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalCancer Letters
Volume217
Issue number1
DOIs
StatePublished - Jan 10 2005

Bibliographical note

Funding Information:
We thank Lisa Adwan for assistance with the manuscript. This work was supported in part by funds from the C.M. Iverson Charitable Trust/American Cancer Society grant RPG0005201CSM to B.W., and Veterans of Foreign Wars and Ladies Auxiliary Cancer Research Center Endowment Fund, the American Society of Colon and Rectal Surgeons Career Development Award, and the Society for University Surgeons Foundation Junior Faculty Award to K.M.B.

Keywords

  • Colon carcinoma cell adhesion
  • Extravasation
  • Mucin
  • O-glycan
  • Sialyl Lewis X

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