基质金属蛋白酶-7调节结肠癌细胞中连接蛋白-2 的细胞外脱落。
The matrix metalloproteinase-7 regulates the extracellular shedding of syndecan-2 from colon cancer cells.
机构信息
Department of Life Sciences, Division of Life and Pharmaceutical Sciences, The Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul 120-750, Republic of Korea.
出版信息
Biochem Biophys Res Commun. 2012 Jan 27;417(4):1260-4. doi: 10.1016/j.bbrc.2011.12.120. Epub 2011 Dec 29.
The cell surface heparan sulfate proteoglycan syndecan-2 regulates the activation of matrix metalloproteinase-7 (MMP-7) as a docking receptor. Here, we demonstrate the role of MMP-7 on syndecan-2 shedding in colon cancer cells. Western blot analysis showed that shed syndecan-2 was found in the culture media from various colon cancer cells. Overexpression of MMP-7 enhanced syndecan-2 shedding, whereas the opposite was true when MMP-7 levels were knocked-down using small inhibitory RNAs. Consistently, HT29 cells treated with MMP-7, but neither MMP-2 nor MMP-9, showed increased shed syndecan-2 in a time- and concentration-dependent manner. Furthermore, MALDI-TOF MS analysis and N-terminal amino acid sequencing revealed that MMP-7 cleaved both recombinant syndecan-2 and an endogenously glycosylated syndecan-2 ectodomain in the N-terminus at Leu(149) residue in vitro. Taken together, the data suggest that MMP-7 directly mediates shedding of syndecan-2 from colon cancer cells.
细胞表面硫酸乙酰肝素蛋白聚糖连接蛋白-2 作为衔接受体调节基质金属蛋白酶-7（MMP-7）的激活。在这里，我们证明了 MMP-7 在结肠癌细胞中连接蛋白-2 脱落中的作用。Western blot 分析表明，各种结肠癌细胞培养物的培养基中均发现有脱落的连接蛋白-2。MMP-7 的过表达增强了连接蛋白-2 的脱落，而当使用小干扰 RNA 降低 MMP-7 水平时则相反。同样，MMP-7 处理的 HT29 细胞而非 MMP-2 或 MMP-9 处理的细胞以时间和浓度依赖的方式显示出脱落的连接蛋白-2 增加。此外，MALDI-TOF MS 分析和 N 末端氨基酸测序表明，MMP-7 在体外将重组连接蛋白-2 和内源性糖基化连接蛋白-2 胞外结构域在 N 端的亮氨酸（149）残基处裂解。总之，这些数据表明 MMP-7 直接介导结肠癌细胞中连接蛋白-2 的脱落。
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