Role of ELAM-1 Binding and Cytokines in Liver Metastasis of Pancreatic Cancer and Possible Therapeutic Application of a Glycosylation Inhibitor

Abstract

In this study, using pancreatic cancer cell lines, we investigated the role of carbohydrate expression, ELAM-1 binding and cytokines in liver metastasis of pancreatic cancer, and the possible therapeutic application of a glycosylation inhibitor. SW1990 cells revealed a high metastatic potential (90%) in the intrasplenic injection model, and this metastatic ability was correlated with its high carbohydrate expression (sialy-Le^a & Le^x) and high adhessiveness to HUVECs and ELAM-1. By coculture of SW1990 cells with peripheral mononuclear leukocytes, high production of TNF-αand IL-1β occurred in the medium, and this medium could induce expression of ELAM-1 on HUVECs. A glycosylation inhibitor (BZN) inhibited carbohydrate expression, ELAM-1 binding and liver metastasis of SW1990. These findings suggest a possible new therapeutic application of BZN for metastasis.