Anti-metastatic effect of the sialyl Lewis-X analog GSC-150 on the human colon carcinoma derived cell line KM12-HX in the mouse.
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 nodules 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 liver was also significantly reduced by GSC-150 co-administration in lipopolysaccharide (LPS)-treated mice at 48 h after administration of the tumor cells, while GSC-150 did not reduce the amount of HX cells distributed at 30 min. Considering our previous report that the initial phase of the distribution of KM12-HX cells in liver is 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-alpha (TNF-alpha)-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 interactions between cancer and host cells.
Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
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Shirota
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Kato
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Irimura
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Kondo
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Sugiyama
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D003110:Colonic Neoplasms / Q000473:pathology*; D006028:Glycosphingolipids / Q000494:pharmacology*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006028:Glycosphingolipids; C104429:GSC 150; D013936:Thymidine