Possible mechanism of inhibition of experimental pulmonary metastasis of mouse colon adenocarcinoma 26 sublines by a sialic acid: nucleoside conjugate.

Abstract

As described previously (I. Kijima-Suda et al., Cancer Res., 46: 858-862, 1986), a sialyltransferase inhibitor, 5-fluoro-2',3'-isopropylidene-5'-O-(4-N-acetyl-2,4-dideoxy-3,6,7,8-tetra -O- acetyl-1-methoxycarbonyl-D-glycero-alpha-D-galactooctapyranosyl)ur idine (KI-8110), inhibits pulmonary metastasis of murine colon adenocarcinoma 26 sublines of high (NL-17) and low (NL-44) metastatic potential. To investigate the mechanism of this inhibition, the effect of KI-8110 on the metastatic cascade, especially on the interaction between tumor cells and platelets which may play a crucial role in tumor cell metastasis, was examined. NL-17 cells induced irreversible platelet aggregation in heparinized human platelet-rich plasma in vitro. This activity was reduced by pretreatment of the tumor cells with KI-8110. Inhibition of aggregation was also induced by the treatment of tumor cells with neuraminidase or Limax flavus agglutinin, a lectin specific for sialic acid. Sialic acid, fucose, sialyllactose, and bovine submaxillary mucin inhibited this tumor cell-induced platelet aggregation, while galactose, mannose, lactose, alpha 1-acid glycoprotein, fetuin, and asialo-bovine submaxillary mucin did not. KI-8110 also inhibited platelet-derived growth factor-dependent growth of NL-17 cells, but showed no effect on insulin or epidermal growth factor-dependent growth of the tumor cells. Platelet-derived growth factor-induced phosphorylation of membrane protein was reduced by treatment of NL-17 cells with KI-8110. The same result was obtained in the neuraminidase-treated membrane fraction of NL-17 cells. These results suggest that KI-8110 inhibits experimental tumor cell metastasis by inhibiting the interaction between tumor cells and host platelets in at least two pathways, and this may be due to a reduction of sialic acid contents of the membrane surface of tumor cells.

• Authors: I Kijima-Suda, T Miyazawa, M Itoh, S Toyoshima, T Osawa
• Journal: Cancer research (Cancer Res) Vol. 48 Issue 13 Pg. 3728-32 (Jul 01 1988) ISSN: 0008-5472 [Print] United States
• PMID: 3288333 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycosides
• Insulin
• Membrane Proteins
• Platelet-Derived Growth Factor
• KI 8110
• Neuraminidase
• Uridine

Topics

• Animals
• Cell Adhesion (drug effects)
• Cell Division (drug effects)
• Glycosides (pharmacology)
• Insulin (pharmacology)
• Membrane Proteins (metabolism)
• Mice
• Neoplasm Metastasis
• Neuraminidase (pharmacology)
• Phosphorylation
• Platelet Aggregation (drug effects)
• Platelet-Derived Growth Factor (pharmacology)
• Tumor Cells, Cultured
• Uridine (analogs & derivatives, pharmacology)