The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, P.R. China.
Oncol Rep. 2010 Jan;23(1):69-78.
MMP-26 is a novel member of the MMP family and is widely expressed in cancer cells of epithelial origin. Published research shows that MMP-26 contributes to tumor development and to the restoration of tissue injury. In this study, in order to identify the functions of MMP-26 that contribute to the biological phenotype and behavior of non-epithelial human glioma U251 cells, we established an MMP-26 overexpressing tumor cell model using gene transfection. We then used these cells to investigate the role of MMP-26 in tumor progression. Adherence and spreading assay, wound healing assay, Boyden chamber invasion assay, and in vivo tumorigenicity assay were performed to analyze the invasion ability of MMP-26 transfected U251 cells. Microvessel density analysis and tumor cell induced angiogenesis assay were employed to detect the function of MMP-26 in angiogenesis. Results showed that the spreading cell ratio of MMP-26 transfected cells was significantly higher than parental U251 cells. The relative migration distance of MMP-26 transfected cells on Matrigel was significantly higher than that of parental U251 cells. The Boyden chamber assay showed that MMP-26 could significantly enhance the ability of U251 cells to invade through Matrigel. MMP-26 could also enhance the local invasion ability of U251 cells in vivo. There was a significant increase of the microvessel density of tumor tissue derived from MMP-26 transfected U251 cells. The vessel numbe induced by MMP-26 transfected U251 cells in nude mice was also significantly higher than that induced by parental U251 cells. In conclusion, we successfully established an MMP-26 overexpressing cell model and confirmed that MMP-26 contributed to U251 cell invasion and migration in vitro. We also demonstrated that MMP-26 plays an important role in local invasion, and angiogenesis.
MMP-26 是基质金属蛋白酶（MMPs）家族的一个新成员，广泛表达于上皮来源的肿瘤细胞中。已发表的研究表明，MMP-26 有助于肿瘤的发展和组织损伤的修复。在这项研究中，为了鉴定 MMP-26 促进非上皮来源的人胶质母细胞瘤 U251 细胞生物学表型和行为的功能，我们通过基因转染建立了 MMP-26 过表达肿瘤细胞模型。然后，我们使用这些细胞来研究 MMP-26 在肿瘤进展中的作用。采用黏附与铺展实验、划痕愈合实验、Boyden 室侵袭实验和体内致瘤性实验分析 MMP-26 转染 U251 细胞的侵袭能力。微血管密度分析和肿瘤细胞诱导血管生成实验用于检测 MMP-26 在血管生成中的功能。结果显示，MMP-26 转染细胞的铺展细胞比例明显高于亲本 U251 细胞。MMP-26 转染细胞在 Matrigel 上的相对迁移距离明显高于亲本 U251 细胞。Boyden 室实验表明，MMP-26 可显著增强 U251 细胞穿过 Matrigel 的能力。MMP-26 还可增强 U251 细胞在体内的局部侵袭能力。MMP-26 转染 U251 细胞来源的肿瘤组织微血管密度明显增加。MMP-26 转染 U251 细胞在裸鼠体内诱导的血管数也明显高于亲本 U251 细胞。总之，我们成功建立了 MMP-26 过表达细胞模型，并证实 MMP-26 促进 U251 细胞体外侵袭和迁移。我们还证明 MMP-26 在局部侵袭和血管生成中发挥重要作用。
