Ganglioside GD1a Negatively Regulates Matrix Metalloproteinase-9 Expression in Mouse FBJ Cell Lines at the Transcriptional Level

Abstract

Mouse FBJ virus-induced osteosarcoma FBJ-S1 cells rich in GD1a are not readily metastatic, whereas FBJ-LL cells with low levels of GD1a are highly metastatic. GD1a was previously shown to suppress metastasis of mouse FBJ cells and to upregulate caveolin-1 and stromal interaction molecule 1 expression. The present study demonstrates that matrix metalloproteinase-9 (MMP-9) expression renders FBJ-LL cells invasive. MMP-9 is inversely regulated by GD1a, based upon four observations: MMP-9 mRNA content was 5 times higher in FBJ-LL cells than FBJ-S1 cells; a GD1a-re-expressing FBJ-LL cell variant produced through beta1,4GalNAcT-1 cDNA transfection expressed lower levels of MMP-9; exogenous addition of GD1a to FBJ-LL cells decreased MMP-9 production in a dose- and time-dependent manner; and treatment of GD1a-rich cells with D-PDMP or siRNA targeting St3gal2 decreased GD1a expression, but augmented MMP-9 expression. This is the first report demonstrating that GD1a negatively regulates expression of MMP-9 at the transcriptional level.

The Antagonistic Actions of Endogenous Interleukin-1β and 15-Deoxy-Δ12,14-prostaglandin J2 Regulate the Temporal Synthesis of Matrix Metalloproteinase-9 in Sheared Chondrocytes

“…Zymography-Gelatinase activity was determined according to a previously described method (22). In brief, the conditioned media of cells were collected and mixed with non-reducing sample buffer containing 0.5 M Tris, pH 6.8, 5% SDS, 20% glycerol, and 1% bromphenol blue in a 1:1 ratio and electrophoresed directly on 10% SDS-polyacrylamide gels (SDS-PAGE).…”

Metastatic Osteosarcoma Gene Expression Differs In Vitro and In Vivo

“…Expression correlates with metastasis [19] MME Absence associated with metastasis [25] MMP9 Suppression by GD1a decreases metastasis [20] N-Cadherin Overexpression suppresses pulmonary metastasis [24] nm23…”

Changing the Nature of Melanoma Cells by Manipulation of Ganglioside Expression

“…Overexpression of the GD3 synthase gene suppresses MMP-9 expression by inhibiting the combination between the MMP-9 promoter and transcription factors (NF-κB and AP-1) in vascular smooth muscle cells (Moon et al, 2004). In murine FBJ cells, GD1a is found to suppress MMP-9 expression at the transcriptional level (Hu et al, 2007). On the other hand, overexpression of plasma membrane-expressed sialidase Neu3 inhibits MMP-9 expression in vascular smooth muscle cells; implying gangliosides promote MMP-9 (Moon et al, 2007).…”

“…These lines of evidence clearly show that PI3K signaling pathway plays an important role in MMP-9 regulation. Reports from several laboratories have concluded that MMP-9 expression is modulated not only by cytokines but also by gangliosides (Hu et al, 2007;Moon et al, 2004;Zhang et al, 2006). GM1, present in the glycolipid-enriched microdomain, is one of the crucial factors regulating cancer metastatic potential via the modulation of MMP-9 localization and secretion, as well as suppression of tumor invasion potential (Zhang et al, 2006).…”