Anti-metastatic effect of the sialyl Lewis-X analog GSC-150 on the human colon carcinoma derived cell line KM12-HX in the mouse

Kazuhiko Shirota, Yukio Kato, Tatsuro Irimura, Hirosato Kondo, Yuichi Sugiyama

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 express 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-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 interactions between cancer and host cells.

Original languageEnglish
Pages (from-to)316-319
Number of pages4
JournalBiological and Pharmaceutical Bulletin
Volume24
Issue number3
DOIs
Publication statusPublished - Apr 5 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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