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

Tetsuji Sawada, Yong-Suk Chung, Nobuya Yamada, Satoshi Takatsuka, Yasuhiro Sakurai, Yuichi Arimoto, Masakazu Yashiro, Shigehiko Nishimura, Teruyoshi Ikeda, Michio Sowa

The First Department of Surgery, Osaka City University Medical School

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-α and 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.

Key words
ELAM-1, cytokine, glycosylation inhibitor

Reprint requests
Tetsuji Sawada The First Department of Surgery, Osaka City University, Medical School
1-5-7 Asahimachi, Abeno-ku, Osaka, 545 JAPAN

Accepted
November 15, 1995

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