Expression of
sialyl Lewis(x) (
sLe(x)) and sLe(a) on
tumor cells is thought to facilitate
metastasis by promoting cell adhesion to
selectins on vascular endothelial cells. Experiments supporting this concept usually bypass the early steps of the metastatic process by employing
tumor cells that are injected directly into the blood. We investigated the relative role of
sLe(x)
oligosaccharide in the dissemination of
breast carcinoma, employing a spontaneous murine
metastasis model. An
sLe(x) deficient subpopulation of the 4T1 mammary
carcinoma cell line was produced by negative selection using the
sLe(x)-reactive KM93 MAb. This subpopulation was negative for
E-selectin binding but retained
P-selectin binding. Both
sLe(x)-negative and -positive cells grew at the same rate; however,
sLe(x)-negative cells spread more efficiently on plates and had greater motility in
wound-scratch assays. Mice inoculated in the mammary fat pad with
sLe(x)-negative and -positive variants produced lung
metastases. However, the number of lung
metastases was significantly increased in the group inoculated with the
sLe(x)-negative variant (p = 0.0031), indicating that negative selection for the
sLe(x)
epitope resulted in enrichment for a subpopulation of cells with a high metastatic phenotype. Cell variants demonstrated significant differences in cellular morphology and pattern of
tumor growth in primary and secondary
tumor sites. These results strongly suggest that loss of
sLe(x) may facilitate the metastatic process by contributing to escape from the primary
tumor mass.