Department of Pathology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
BMC Cancer. 2011 Jul 17;11:300. doi: 10.1186/1471-2407-11-300.
Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP) production by adjacent stromal cells. Its first Ig domain (ECI) contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active.
The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production.
ECI carrying a chitobiose unit, ECI-(GlcNAc) 2, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man)3(GlcNAc)2], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc)2.
Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.
Emmprin 是一种含有两个 Ig 结构域的糖蛋白，在肿瘤细胞表面丰富，并刺激相邻基质细胞产生基质金属蛋白酶（MMP）。其第一个 Ig 结构域（ECI）含有生物活性位点。Emmprin 活性对 N-糖基化的依赖性存在争议。我们研究了是否具有最短糖链的合成 ECI 具有功能活性。
通过硫酯法合成了带有糖链、壳二糖单元或 N-连接核心五糖的完整 ECI 肽，并将其添加到成纤维细胞中，以检查它们是否刺激 MMP-2 的产生。
携带壳二糖单元的 ECI（GlcNAc）2，但不携带壳二糖单元或仅携带壳二糖单元的 ECI，可剂量依赖性地刺激成纤维细胞中 MMP-2 的产生。带有更长壳二糖单元的 ECI（（Man）3（GlcNAc）2）也刺激 MMP-2 的产生，但刺激程度低于 ECI（GlcNAc）2。
我们的结果表明，当用 N-糖基化起始的二糖壳二糖替代时，ECI 可以模拟 emmprin 活性。
