The role of sialylated Lewis antigens on hematogeneous metastases of human pancreas 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 not the role of SLe(a)/SLe(x) antigens on hematogenous metastasis to the liver in SCID mice was exclusively mediated by adhesion by using antibodies for these antigens and SLe(a)/SLEx-negative, human pancreas adenocarcinoma cell 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 attachment augmentation to activated endothelial cells. PCI-B cells are xenotransplantable 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 establishment and growth of metastatic colonies when anti-SLe(a) or anti-SLe(x) antibody was administered. This indicates that SLe(a/x) antigens have an important 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) antigens other than that of the attachment between turner and endothelial cells.