Ganglioside GD1a negatively regulates matrix metalloproteinase-9 expression in mouse FBJ cell lines at the transcriptional level.
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.
Hu
Dan
D
Laboratory of Tumor Biology and Glycobiology, Shenyang Pharmaceutical University, Shenyang, P. R. China.
Man
Zhiqiu
Z
Wang
Pu
P
Tan
Xuan
X
Wang
Xiaodong
X
Takaku
Shizuka
S
Hyuga
Sumiko
S
Sato
Toshinori
T
Yao
Xinsheng
X
Yamagata
Sadako
S
Yamagata
Tatsuya
T
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005732:Gangliosides / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*
D005732:Gangliosides; D009025:Morpholines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C021298:ganglioside, GD1a; C033110:RV 538; D020780:Matrix Metalloproteinase 9