Hu Dan, Man Zhiqiu, Wang Pu, Tan Xuan, Wang Xiaodong, Takaku Shizuka, Hyuga Sumiko, Sato Toshinori, Yao Xinsheng, Yamagata Sadako, Yamagata Tatsuya
Laboratory of Tumor Biology and Glycobiology, Shenyang Pharmaceutical University, Shenyang, P. R. China.
Connect Tissue Res. 2007;48(4):198-205. doi: 10.1080/03008200701458731.
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.
富含GD1a的小鼠FBJ病毒诱导的骨肉瘤FBJ - S1细胞不易发生转移，而GD1a水平较低的FBJ - LL细胞具有高度转移性。先前研究表明，GD1a可抑制小鼠FBJ细胞的转移，并上调小窝蛋白 - 1和基质相互作用分子1的表达。本研究表明，基质金属蛋白酶 - 9（MMP - 9）的表达使FBJ - LL细胞具有侵袭性。基于以下四点观察结果，MMP - 9受GD1a的反向调节：FBJ - LL细胞中MMP - 9 mRNA含量比FBJ - S1细胞高5倍；通过β1,4GalNAcT - 1 cDNA转染产生的重新表达GD1a的FBJ - LL细胞变体表达较低水平的MMP - 9；向FBJ - LL细胞外源性添加GD1a以剂量和时间依赖性方式降低MMP - 9的产生；用D - PDMP或靶向St3gal2的siRNA处理富含GD1a的细胞可降低GD1a表达，但增加MMP - 9表达。这是第一份证明GD1a在转录水平上负调节MMP - 9表达的报告。
