Expression of emmprin by oral squamous cell carcinoma.
Expression of emmprin by oral squamous cell carcinoma.
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DOI：
10.1002/(sici)1097-0215(20000201)85:3
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发表时间：
2000
影响因子：
6.4
通讯作者：
L. Bordador;X. Li;B. Toole;B. Chen;J. Regezi;L. Zardi;Y. Hu;D. M. Ramos
中科院分区：
文献类型：
--
作者：
L. Bordador;X. Li;B. Toole;B. Chen;J. Regezi;L. Zardi;Y. Hu;D. M. Ramos
最近在一些肿瘤细胞上鉴定的跨膜糖蛋白，细胞外基质金属蛋白酶诱导剂（EMMPRIN），已被证明可诱导瘤周成纤维细胞（PTF）产生金属蛋白酶（MMP）。我们检测了正常人口腔粘膜和口腔鳞状细胞癌（SCC）活检标本中EMMPRIN的表达。在正常粘膜中，EMMPRIN表达于整个上皮的细胞膜上，沿基底细胞层沿着轻微增强。在口腔鳞状细胞癌中，EMMPRIN在整个病变的细胞膜上表达。免疫荧光显微镜定位EMMPRIN的细胞膜在一个高度侵袭性的口腔鳞状细胞癌细胞系与我们在体内的观察。EMMPRIN的功能阻断抗体显著抑制口腔SCC细胞在腱生蛋白-C（TN-C）和纤连蛋白上的迁移以及通过重建基底膜（RBM）的侵袭。我们以前表明，SCC细胞和PTF的可溶性因子是TN-C基质沉积所必需的。为了确定EMMPRIN是否可以调节这些可溶性因子的释放或表达，我们再次使用功能阻断抗体。EMMPRIN抗体完全抑制TN-C基质的组织化，并部分减少口腔SCC细胞/PTF共培养物中FN基质的沉积。此外，EMMPRIN抗体干扰MMP-2的表达。此外，MMP-2抗体干扰口腔鳞状细胞癌细胞侵袭RBM约。百分之七十五我们的研究结果表明，EMMPRIN在口腔鳞状细胞癌中高度表达，促进肿瘤细胞的运动，并介导TN-C基质沉积。总之，这些结果表明，EMMPRIN可能有助于调节口腔鳞状细胞癌的侵袭。
A transmembrane glycoprotein recently identified on some tumor cells, extracellular matrix metalloproteinase inducer (EMMPRIN), has been shown to induce metalloproteinase (MMP) production by peritumor fibroblasts (PTF). We examined biopsy specimens of normal human oral mucosa and oral squamous cell carcinoma (SCC) for expression of EMMPRIN. In normal mucosa, EMMPRIN was expressed at the cell membrane throughout the epithelium with a slight enhancement along the basal cell layer. In oral SCC, EMMPRIN was expressed at the cell membrane throughout the entire lesion. Immunofluorescence microscopy localized EMMPRIN to the cell membrane in a highly invasive oral SCC cell line in agreement with our in vivo observations. Function-blocking antibodies to EMMPRIN significantly inhibited oral SCC cell migration on tenascin-C (TN-C) and fibronectin as well as invasion through a reconstituted basement membrane (RBM). We previously showed that soluble factors from SCC cells and PTF are required for deposition of a TN-C matrix. To determine whether EMMPRIN may modulate the release or expression of these soluble factors, we again used function-blocking antibodies. Antibodies to EMMPRIN completely inhibited the organization of TN-C matrices and partially reduced the deposition of FN matrices by oral SCC cell /PTF co-cultures. In addition, antibodies to EMMPRIN perturbed the expression of MMP-2. Moreover, antibodies to MMP-2 perturbed oral SCC cell invasion of an RBM by approx. 75%. Our results demonstrate that EMMPRIN is highly expressed in oral SCC, facilitates tumor cell motility, and mediates TN-C matrix deposition. Taken together, these results suggest that EMMPRIN may help regulate oral squamous cell carcinoma invasion.