Synthetic emmprin peptides inhibit tumor cell-fibroblast interaction-stimulated upregulation of MMP-2 and tumor cell invasion
Synthetic emmprin peptides inhibit tumor cell-fibroblast interaction-stimulated upregulation of MMP-2 and tumor cell invasion
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DOI：
10.3892/ijo.2011.1060
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发表时间：
2011-09-01
影响因子：
5.2
通讯作者：
Nabeshima, Kazuki
中科院分区：
文献类型：
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作者：
Koga, Kaori;Aoki, Mikiko;Nabeshima, Kazuki
基质细胞是人类癌组织中基质金属蛋白酶（MMP）的主要来源。 Emmprin 是一种糖基化跨膜蛋白，含有两个免疫球蛋白 (IQ) 结构域，在癌细胞中表达并刺激邻近基质细胞产生 MMP。 Emmprin 的第一个 Ig 结构域 (ECI) 包含生物活性位点。我们研究了携带部分 ECI 序列的合成肽是否可以抑制 emmprin 活性。在成纤维细胞和几种不同的人类肿瘤细胞类型（包括癌、肉瘤、黑色素瘤、白血病和神经胶质瘤细胞）的共培养物中，只有第二个肽 (emp#2)（包含推定的 N-糖基化位点序列）抑制 emmprin 刺激的 MMP-2 产生。此外，emp#2 显着抑制由与成纤维细胞相互作用促进的胶质母细胞瘤细胞的侵袭活性。该肽对 Emmprin 活性的干扰可能在预防 MMP-2 依赖性癌症侵袭方面具有潜在的治疗用途。
Stromal cells are the main source of matrix metalloproteinases (MMPs) in human carcinoma tissues. Emmprin is a glycosylated transmembrane protein containing two immunoglobulin (IQ) domains that is expressed in carcinoma cells and stimulates MMP production by adjacent stromal cells. The first Ig domain (ECI) of emmprin contains the biologically active site. We investigated whether synthetic peptides carrying a partial ECI sequence could inhibit emmprin activity. Only the second peptide (emp#2), which contains a putative N-glycosylation site sequence, inhibited emmprin-stimulated production of MMP-2 in co-cultures of fibroblasts and several different human tumor cells types, including carcinoma, sarcoma, melanoma, leukemia and glioma cells. Moreover, emp#2 significantly inhibited the invasive activity of glioblastoma cells promoted by interaction with fibroblasts. Perturbation of emmprin activity by this peptide may have potential therapeutic uses in the prevention of MMP-2-dependent cancer invasion.