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

Int J Cancer. 2000 Oct 1;88(1):53-7. doi: 10.1002/1097-0215(20001001)88:1<53::aid-ijc8>3.0.co;2-7.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

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