E-, P-, and
L-selectin support the adhesion of leukocytes to the vessel wall through the recognition of specific
carbohydrate ligands, which often contain sialylated, fucosylated lactosamines such as
sialyl Lewis x [sLex; Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-].
E-selectin expressed by activated endothelium has been shown to support the adhesion of sLex-bearing
colon cancer cells. In the present study, we examine the interactions of multiple
colon cancer cell lines with all three
selectins. Three
colon cancer cell lines (LS 180, T84, and COLO 205) bound to recombinant purified E-, P-, and
L-selectin. The
colon cancer line COLO 320 bound to P- and
L-selectin but not
E-selectin; conversely, HT-29 cells bound
E-selectin but not P- and
L-selectin. Caco-2 showed little or no interaction with any of the three
selectins. Treatment of the cells with O-
sialoglycoprotease from Pasteurella haemolytica, an
enzyme that selectively cleaves
mucin-type O-linked
glycoproteins, reduced binding to purified P- and
L-selectin in all cases. In addition, recombinant soluble P- and
L-selectin bound to affinity-purified
mucins from all adherent tumor cell lines. Of the four tumor cell lines that interacted with
E-selectin, O-glycoprotease treatment substantially diminished adhesion of LS 180 and T84, had little effect on COLO 205, and failed to inhibit the binding of HT-29. As predicted by these data,
E-selectin showed substantial binding only to
mucins purified from LS 180 and T84. These findings suggest that L- and
P-selectin interact primarily with
mucin-type
ligands on
colon cancers, whereas
E-selectin can recognize both
mucin and nonmucin
ligands. Binding of the
colon cancer lines to purified
selectins correlates with their adhesion to activated endothelial cells (
E-selectin-dependent), platelets (
P-selectin-dependent), and neutrophils (
L-selectin-dependent). These differential
tumor cell-
selectin interactions may influence metastatic spread and may also contribute to the observed variability in host response to
tumor progression.