TY - JOUR
T1 - Reduced cell migration, tumor growth and experimental metastasis of rat F-11 cells whose expression of GD3-synthase is suppressed
AU - Zeng, Guichao
AU - Gao, Luoyi
AU - Yu, Robert K.
PY - 2000
Y1 - 2000
N2 - 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. (C) 2000 Wiley-Liss, Inc.
AB - 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. (C) 2000 Wiley-Liss, Inc.
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U2 - 10.1002/1097-0215(20001001)88:1<53::AID-IJC8>3.0.CO;2-7
DO - 10.1002/1097-0215(20001001)88:1<53::AID-IJC8>3.0.CO;2-7
M3 - Article
C2 - 10962439
AN - SCOPUS:0033851103
SN - 0020-7136
VL - 88
SP - 53
EP - 57
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 1
ER -