Diverse Effects Of Ganglioside Gd1a On Mmp-9 Regulation In Different Cell Lines

Matrix metalloproteinase-9 (MMP-9) but not MMP-2 expression has been shown to be negatively regulated by exogenous ganglioside GD1a in FBJ cell lines. In GM3 synthase St3gal5 siRNA and GD1a synthase St3gal2 siRNA transfected Lewis cells, MMPs expression was increased, suggesting that GM3 or GD1a can suppress MMP-9 expression. So we added exogenous ganglioside GD1a to mouse lung cancer Lewis cells, human HeLa cells and THP-1 cells, and found that MMP-9 was stimulated at the transcriptional and translational levels as in the case of FBJ cell lines. However, in mouse melanoma B16 cells, MMP-9 was positively regulated by exogenous GD1a at the transcriptional level. In order to verify how GD1a regulates MMP-9, we compared mouse Lewis cells and mouse melanoma B16 cells.In Mouse melanoma B16 cells did not contain GD1a, but GM3 as a main ganglioside as revealed by HPTLC, while Lewis cells contained GD1a. Zymography Revealed that Lewis cells secreated much more MMPs than B16 cells. Beacause of difference in the contents of MMP-9 in these two cell lines, we got the hypothesis that GD1a regulates MMP-9 through different pathway in these cell lines. The results revealed that in B16 cells, GD1a signals were mediated partly by caveolae, and mainly through ERK for inducing MMP-9 expression; in Lewis cells, GD1a signals were not mediated by caveolae, but partly through p38, ERK and JNK pathway. The results also showed that TNF-αmainly through ERK regulate MMP-9 expression in B16 cells, and in Lewis cells TNF-αpartly through p38 , ERK and JNK pathway. Thus, we conclude that ganglioside GD1a activites different signal pathways in different cell types.