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Ganglioside GD1 Functions in the Adhesion of Metastatic Tumor Cells to Endothelial Cells of the Target Tissue¹

Department of Biochemistry, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku 113 Tokyo, [T. T., D. I., M. O., S. H.], and Bio-organic Research Department, International Research Laboratories, Ciba-Geigy Japan Limited, 10-66 Miyuki-Cyo, Takarazuka, Hyogo 665 [M. N.], Japan

We studied the role of glycosphingolipids expressed on the cell surfaces of a metastatic tumor cell line. Glycosphingolipid compositions of the low-metastatic murine lymphosarcoma cell line RAW117-P and its subline, RAW117-H10, which shows higher metastatic potential for the liver than P cells, were compared. Both types of cells had LacCer, Gg₃Cer, and Gg₄Cer as the major neutral glycosphingolipids and GM1b and GD1 as the gangliosides. There are differences in glycosphingolipid contents, the neutral glycosphingolipid contents in the parental cells being 1.5-fold higher than that in the variant ones. In contrast, the level of GD1 in H10 cells was twice as much as that in the P cells; however, the expression of other gangliosides was down-regulated. On the basis of the results of glycosphingolipid analysis, we investigated the functional role of GD1 in H10 cells in the adhesion of the tumor cells to the target tissue by using hepatic sinusoidal endothelial (HSE) cells. GD1 and GM1b inhibited the adhesion when HSE cells were incubated prior to coculture with the tumor cells. This inhibitory effect by GD1 and GM1b was observed within 30 min after addition of H10 cells to HSE cells and was dose dependent. GD1 showed a higher inhibitory effect on the adhesion than GM1b, whereas other glycosphingolipids showed no inhibitory effect. Anti-GD1 monoclonal antibody also inhibited the adhesion between the H10 and HSE cells. When cultured without fetal bovine serum for 30 min in a various glycosphingolipids-coated dish for bacterial culture, HSE cells adhered to the area coated with GD1 but not to areas coated with other glycosphingolipids. HSE cell adhesion depended on the amount of GD1 coated on the plate. These data indicate that GD1 functions as an adhesion molecule in the process of metastasis of H10 cells.

¹ This study was supported in part by the Special Coordination Fund from the Science and Technology Agency of the Japanese Government.

² To whom requests for reprints should be addressed. Phone: 81-886-65-2272; Fax: 81-886-65-5662; E-mail: t_taki@research.otsuka.CO.JP.

³ Present address: Cellular Technology Institute, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-01, Japan.

Received 11/ 5/96. Accepted 3/24/97.

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