WISP-1 overexpression upregulates cell proliferation in human salivary gland carcinomas via regulating MMP-2 expression
WISP-1 overexpression upregulates cell proliferation in human salivary gland carcinomas via regulating MMP-2 expression
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DOI：
10.2147/ott.s107166
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发表时间：
2016-01-01
影响因子：
4
通讯作者：
Zhou, Xiao-Li
中科院分区：
文献类型：
--
作者：
Li, Fu-Jun;Wang, Xin-Juan;Zhou, Xiao-Li
背景资料：WISP-1是CCN生长因子家族的成员，并且已经报道通过经由整合素信号传导触发下游事件在肿瘤发生中发挥重要作用。方法：采用免疫组化、Western blotting和实时荧光定量PCR方法检测WISP-1在人涎腺癌（saliphaticglandcarcinoma，SGC）组织中的表达，并分析WISP-1对SGC A-253细胞生长的调控作用。结果：21例胃癌组织中有15例WISP-1在mRNA和蛋白水平上表达上调，而非癌组织中有5例表达上调，且与淋巴结清扫和骨浸润有关。体外CCK-8法和集落形成法显示外源性WISP-1处理或WISP-1过表达促进A-253细胞生长。此外，我们证实WISP-1过表达上调了A-253细胞中MMP-2的表达，并且MMP-2敲低减弱了WISP-1介导的A-253细胞生长促进作用。我们发现WISP-1在人SGCs中过表达，WISP-1过表达通过上调MMP-2表达促进涎腺细胞增殖。我们的研究认识到WISP-1在人类SGCs中的致癌作用，这可能成为抗癌治疗的潜在靶点。
Background: WISP-1 is a member of the CCN family of growth factors and has been reported to play an important role in tumorigenesis by triggering downstream events via integrin signaling. However, little is known about the role of WISP-1 in proliferation of salivary gland carcinoma (SGC) cells.Methods: In this study, we investigated the WISP-1 expression in SGC tissues via immunohistochemical staining, Western blotting assay, and real-time quantitative polymerase chain reaction method, and then evaluated the regulatory role of WISP-1 in the growth of SGC A-253 cells. In addition, the role of MMP-2 in the WISP-1-mediated growth regulation was also investigated.Results: It was demonstrated that the WISP-1 expression was upregulated at both mRNA and protein levels in 15 of 21 SGC tumor tissues, compared to the non-tumor tissues (five of 21), associated with the lymph node dissection and bone invasion. The in vitro CCK-8 assay and colony-forming assay demonstrated that the exogenous WISP-1 treatment or the WISP-1 overexpression promoted the growth of A-253 cells. In addition, we confirmed that the WISP-1 overexpression upregulated the MMP-2 expression in A-253 cells with the gain-of-function and loss-of-function strategies, and that the MMP-2 knockdown attenuated the WISP-1-mediated growth promotion of A-253 cells.Conclusion: We found that WISP-1 was overexpressed in the human SGCs, and the WISP-1 overexpression promoted the salivary gland cell proliferation via upregulating MMP-2 expression. Our study recognized the oncogenic role of WISP-1 in human SGCs, which could serve as a potential target for anticancer therapy.