Secreted frizzled related protein (sFRP)-2 inhibits bone formation and promotes cell proliferation in ameloblastoma
Secreted frizzled related protein (sFRP)-2 inhibits bone formation and promotes cell proliferation in ameloblastoma
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DOI：
10.1016/j.oraloncology.2009.02.001
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发表时间：
2009-10-01
期刊：
影响因子：
4.8
通讯作者：
Nagatsuka, Hitoshi
中科院分区：
文献类型：
--
作者：
Sathi, Gulsan Ara;Inoue, Miho;Nagatsuka, Hitoshi
Wnt拮抗剂分泌型卷曲相关蛋白（sFRP）-2在成釉细胞瘤的间质细胞和肿瘤细胞中均有强表达。本研究的目的是评估肿瘤细胞分泌的sFRP-2是否在抑制骨形成中具有任何直接作用。本研究使用了在成釉细胞瘤衍生细胞系（AM-1CM）的条件培养基中培养的前成骨细胞系KUSA/A1细胞。进行碱性磷酸酶（ALP）活性、茜素红染色、矿物质定量和MTS测定。Wnt经典通路是成骨细胞的主要通路。通过免疫组织化学和蛋白质印迹分析检测该途径的拮抗剂sFRP-1、2和3。AM-1CM培养的KUSA/A1细胞增殖旺盛，ALP活性低，无矿化基质沉积。sFRP-2在成釉细胞瘤组织和AM-1细胞中呈强表达。sFRP-2耗竭后，细胞显示弥漫性矿化。在本研究中，证实成釉细胞瘤细胞通过在细胞培养模型中分泌sFRP-2而在骨形成减少中具有主要作用。虽然sFRP-2对肿瘤的进展有很大的影响，但抑制sFRP-2的抗骨形成活性和细胞增殖活性可能会降低成釉细胞瘤的侵袭性和复发率。(C)2009爱思唯尔有限公司保留所有权利。
Secreted frizzled related protein (sFRP)-2, a Wnt antagonist, was strongly expressed by both stromal and tumor cells of ameloblastoma. The aim of this study is to evaluate whether sFRP-2 secreted from tumor cells have any direct role in suppressed bone formation or not. A pre-osteoblastic cell line, KUSA/A1 cells, cultured in conditioned medium of an ameloblastoma-derived cell line (AM-1CM) was used in the study. Alkaline phosphatase (ALP) activity, alizarin red staining, mineral quantification and MTS assay was performed. Wnt-canonical pathway is a major pathway for osteoblasts. Antagonists of this pathway, sFRP-1, 2 and 3, were detected by immunohistochemistry and western blot analysis. KUSA/A1 cells cultured in AM-1CM showed high cell proliferation, low ALP activity without mineralized matrix deposition. sFRP-2 was strongly expressed in ameloblastoma tissue and AM-1 cells. After sFRP-2 depletion, the cells showed diffuse mineralization. In this study, it was confirmed that ameloblastoma cells have a major role in decreased bone formation by secreting sFRP-2 in cell culture model. Though, sFRP-2 has great effect on tumor progression, inhibition of sFRP-2's anti-bone formation activity and cell proliferative activity may reduce the invasive property of ameloblastoma and possibility of recurrence rate. (C) 2009 Elsevier Ltd. All rights reserved.