A novel ameloblastoma cell line (AM-3) secretes MMP-9 in response to Wnt-3a and induces osteoclastogenesis
A novel ameloblastoma cell line (AM-3) secretes MMP-9 in response to Wnt-3a and induces osteoclastogenesis
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DOI：
10.1016/j.oooo.2013.03.005
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发表时间：
2013-06-01
影响因子：
2.9
通讯作者：
Kishida, Shosei
中科院分区：
文献类型：
--
作者：
Kibe, Toshiro;Fuchigami, Takao;Kishida, Shosei
Objective.成釉细胞瘤具有高的骨侵袭和局部复发的风险。然而，成釉细胞瘤的骨侵袭机制仍不清楚。在这项研究中，我们建立了一个实验模型，基质金属蛋白酶（MMP）的诱导和破骨细胞生成使用成釉细胞瘤来源的细胞。我们建立了一个不含病毒基因的成釉细胞瘤细胞系，通过实时逆转录-聚合酶链反应分析了所有Wnt和Frizzled成员以及MMP的表达，并通过凝胶内明胶酶分析分析了MMP-2和MMP-9的活性。AM-3，新建立的成釉细胞瘤衍生细胞保留原代培养的成釉细胞瘤细胞的形态。AM-3细胞过度表达Wnt-5a、Frizzled-2、MMP-2和MMP-9的信使RNA，并显示出破骨细胞生成的潜力。另外，Wnt-3a诱导AM-3细胞MMP-9的表达和活化。我们的研究表明AM-3细胞保留了成釉细胞瘤的特征，而没有获得癌细胞的典型特征。此外，Wnt信号在成釉细胞瘤细胞中诱导MMP-9。
Objective. Ameloblastoma has a high risk of bone invasion and local recurrence. However, the mechanisms of bone invasion in ameloblastoma remain unclear. In this study, we established an experimental model for matrix metalloproteinase (MMP) induction and osteoclastogenesis using ameloblastoma-derived cells.Study design. We established an ameloblastoma-derived cell line without viral genes and analyzed the expression of all Wnt and Frizzled members and MMPs by real-time reverse transcription-polymerase chain reaction, and analyzed the activity of MMP-2 and MMP-9 by the in-gel-gelatinase assay.Results. AM-3, newly established ameloblastoma-derived cells retained the morphology of primary-cultured ameloblastoma cells. AM-3 cells overexpressed the messenger RNA of Wnt-5a, Frizzled-2, MMP-2, and MMP-9 and showed the potential of osteoclastogenesis. In addition, Wnt-3a-treatment induced expression and activation of MMP-9 in AM-3 cells.Conclusions. Our study suggests that AM-3 cells retained the characteristics of ameloblastoma, without acquiring typical features of cancer cells. Furthermore, Wnt signaling induced MMP-9 in ameloblastoma cells.