Reduced cell migration, tumor growth and experimental metastasis of rat F-11 cells whose expression of GD3-synthase is suppressed.

Abstract

We previously established a rat F-11 cell line whose expression of ganglioside GD3 was inhibited by stable transfection of the anti-sense vector against the GD3-synthase gene, showing that specific inhibition of GD3-synthase expression in tumor cells greatly reduced their growth rate in nude mice. Here, we report that down-regulation of GD3-synthase expression in anti-sense-transfected F-11 cells correlates with reduced cell migration and invasion in vitro and tumor growth and metastasis in vivo. When cultures were denuded of cells in a 1-mm-wide strip, the anti-sense-transfected F-11 cells migrated very slowly into the denuded area. Differences in migration between anti-sense-transfected cells and control parental cells were easily apparent. In vitro invasion assay of F-11 cells revealed a 3-fold decrease in invasion ability from the GD3-synthase-suppressed cells; colony formation in soft agar was not affected. Injection (i.v.) of control sense-transfected and untransfected F-11 cells resulted in multiple, large metastatic nodules in each of the 12 mice, whereas i.v. injection of anti-sense-transfected F-11 cells formed a single, small metastatic nodule in only 2 of the 8 nude mice. In addition, even if metastasis occurred, the anti-sense-induced metastatic nodules were much smaller than the metastatic nodules formed by control F-11 cells. These results demonstrate that suppression of GD3-synthase expression, which results primarily in a marked decrease in the concentration of ganglioside GD3, greatly reduces cell spreading, invasion and both the incidence and growth rate of experimental metastasis of F-11 cells.

• Authors: G Zeng, L Gao, R K Yu
• Journal: International journal of cancer (Int J Cancer) Vol. 88 Issue 1 Pg. 53-7 (Oct 01 2000) ISSN: 0020-7136 [Print] United States
• PMID: 10962439 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2000 Wiley-Liss, Inc.

Chemical References

• DNA, Antisense
• Gangliosides
• ganglioside, GD3
• Sialyltransferases
• alpha-N-acetylneuraminate alpha-2,8-sialyltransferase

Topics

• Animals
• Cell Division (physiology)
• Cell Line, Transformed
• Cell Movement (physiology)
• DNA, Antisense (genetics, pharmacology)
• Female
• Ganglia, Spinal
• Gangliosides (biosynthesis, metabolism)
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Male
• Mice
• Mice, Nude
• Neoplasm Metastasis
• Neoplasm Transplantation
• Neoplasms, Experimental (enzymology, genetics, pathology)
• Neuroblastoma
• Rats
• Sialyltransferases (antagonists & inhibitors, biosynthesis, genetics)
• Transfection