Tumor cells can invade and generate
metastasis via either lymphatics or blood vessels. When
tumor cells are circulating in the blood, they must adhere to the vessel wall, which is lined by endothelium, before they can extravasate and form new
metastases. Several families of adhesion molecules have been identified to play a role in the extravasation cascade.
Selectins and their
sialyl Lewis(x) and/or
sialyl Lewis(a) (
sLe(x) and sLe(a), respectively) containing
ligands play an initiating role in this cascade; we have now analyzed their role in the generation of metastatic
breast carcinoma lesions. We examined expression of endothelial E- and
P-selectin, expression of epithelial and endothelial
sLe(x) and sLe(a) normal tissues compared with primary and metastatic breast in
carcinoma lesions within individual patients. While normal breast epithelial cells do not express
sLe(x) or sLe(a), epithelial expression of these
oligosaccharide epitopes was enhanced in primary
breast carcinoma lesions. Furthermore, epithelial expression levels of
sLe(x) and/or sLe(a) were even higher in most patients (9 of 12) who had metastatic compared with primary lesions. We show that endothelia in primary lesions express more
sLe(x) than in normal tissue and that metastatic lesions express even higher amounts of
sLe(x) compared with primary lesions. The expression of P- and
E-selectin was also greatly enhanced in
tumor-bearing tissue compared with normal tissue. Our data support the hypothesis that while they are circulating in the blood,
sLe(x)- and/or sLe(a)-expressing
carcinoma cells have a higher probability for extravasation at sites where the endothelium expresses E- and
P-selectin and for generation of new
metastases.