Anti-metastatic Effect of the Sialyl Lewis-X Analog GSC-150 on the Human Colon Carcinoma Derived Cell Line KM12-HX in the Mouse

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We investigated the inhibitory effect of the sialyl Lewis-X(sLeX)analog, GSC-150, on hepatic metastasis of the human colon carcinoma derived cell line, KM12-HX, which highly expresses sLeX antigen on the cell surface. The number of cancer nodeles found in BALB/c nude mouse liver 6 weeks after intrasplenic injection of KM12-HX cells was significantly reduced by co-administration of GSC-150. The amount of [^3H]thymidine-labeled KM12-HX cells distributed in liveer was also sifnificantly reduced by GSC-150 co-administratiion in lipopolysaccharide(LPS)-treated mice at 48h after administration of the tumor cells, while GSC-150 did not reduce the amount of HX cells distributed at 30min. Considering our previous report that the intial phase of the distribution of KM12-HX cell in liveris governed by their being trapped in the hepatic microvessels because of their large size(Mizuno et al., J.Hepatol., 28, 865-877, 1998), these results suggest that GSC-150 does not inhibit this first-pass trapping by microvessels, but inhibits the subsequent process which is more directly related to final metastasis. GSC-150 inhibited the adhesion of KM12-HX cells to tumor necrosis factor-α(TNF-α)-activated human umbilical vein endothelial cells(HUVECs). These findings imply that the anti-metastatic effect of GSC-150 in vivo could be explained by its inhibition of cell-cell interacitions between cancer and host cells.
公益社団法人日本薬学会の論文
2001-03-01

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