The role of sialylated Lewis antigens on hematogeneous metastases of humanpancreas carcinoma cell lines in vivo

Previous studies have shown that sialyl Lewis a (SLe(a)) and sialyl Lewis x (SLe(x)) correlated to hematogeneous metastasis of human cancers. Although SLe(a)/SLe(x) and E-selectin act as a set of adhesion molecules in vitro, it is not clear whether the in vivo correlation is exclusively mediated by the adhesion function, To address this issue, we investigated whether or no t the role of SLe(a)/SLe(x) antigens on hematogenous metastasis to the live r in SCID mice was exclusively mediated by adhesion by using antibodies for these antigens and SLe(a)/SLEx-negative, human pancreas adenocarcinoma cel l line PCI-6. The absence of SLe(a)/SLe(x) expression was supported by the absent flow cytometric detection of the antigens as well as by the absent a ttachment augmentation to activated endothelial cells. PCI-B cells are xeno transplantable to nude and SCID mice and produce vascular endothelial cell growth factor (VEGF) in a significant amount. PCI-B cells, 1 x 10(6), were injected into the spleens of SCID mice, and resultant liver metastases were evaluated six weeks later. We observed an inhibitory effect on the establi shment and growth of metastatic colonies when anti-SLe(a) or anti-SLe(x) an tibody was administered. This indicates that SLe(a/x) antigens have an impo rtant in vivo role, even in the metastasis of SLe(a)/SLe(x)-negative tumor cells. This implies that there may be an in vivo function of SLe(a/x) antig ens other than that of the attachment between turner and endothelial cells.