ENHANCED EXPRESSION OF ALPHA(1,3)FUCOSYLTRANSFERASE GENES CORRELATES WITH E-SELECTIN-MEDIATED ADHESION AND METASTATIC POTENTIAL OF HUMAN LUNG ADENOCARCINOMA CELLS
M. Martinsatue et al., ENHANCED EXPRESSION OF ALPHA(1,3)FUCOSYLTRANSFERASE GENES CORRELATES WITH E-SELECTIN-MEDIATED ADHESION AND METASTATIC POTENTIAL OF HUMAN LUNG ADENOCARCINOMA CELLS, Cancer research, 58(7), 1998, pp. 1544-1550
alpha(1,3)- and alpha(1,4)-fucosylated oligosaccharides such as sialyl
-Lewis(x) (sialyl-Le(x)) and sialyl-Lewis(a) (sialyl-Le(a)) have been
reported to participate in tumor cell adhesion to activated endotheliu
m, We examined bg cytofluorometry the expression of Le(x), sialyl-Le(x
), sialyl-Le(x) dimeric, Le(a), and sialyl-Le(a) on the surface of two
human lung adenocarcinoma cell lines with different lung colonization
potential. High expression levels of all of these antigens were detec
ted in the metastatic HAL-8Luc cells, whereas the closely related nonm
etastatic HAL-24Luc cells only expressed the sialyl-Le(a) and sialyl-L
e(x) dimeric antigens, both at lower level than in HAL-8Luc cells, Fiv
e alpha(1,3)-fucosyltransferases (alpha(1,3)-Fuc-T) controlling the sy
nthesis of these molecules hare been identified to date (Fuc-TIII-Fuc-
IVII). The expression of these five genes was also higher in the metas
tatic cells than in the nonmetastatic counterparts as was shown by Nor
thern blot analysis. In vitro adhesion assays showed that only the met
astatic cell line adheres significantly to E-selectin-expressing human
endothelial cells. Moreover, monoclonal antibody (mAb) blockade of E-
selectin completely abolished tumor cell binding. Adhesion inhibition
experiments using mAbs against sialylated fucosylated oligosaccharides
expressed on tumor cells indicated that these antigens are involved i
n the binding, Anti-sialyl-Lex(x) mAb (CSLEX-1) inhibited adhesion by
85%; it had the most pronounced inhibitory effect. These findings sugg
est that the overexpression of alpha(1,3)-Fuc-T genes in the metastati
c HAL-8Luc cells, compared with HAL-24Luc cells, results in an enhance
d surface display of fucosylated oligosaccharides, which contributes t
o the adhesive capacity of these cells to the activated endothelium an
d correlates with their lung colonization potential.