MCP-1 as a Potential Target to Inhibit the Bone Invasion by Oral Squamous Cell Carcinoma
MCP-1 as a Potential Target to Inhibit the Bone Invasion by Oral Squamous Cell Carcinoma
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DOI：
10.1002/jcb.24849
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发表时间：
2014-10-01
影响因子：
4
通讯作者：
Gao, Jin
中科院分区：
文献类型：
--
作者：
Quan, Jingjing;Morrison, Nigel A.;Gao, Jin
骨侵袭是口腔鳞状细胞癌（OSCC）的常见并发症，本研究旨在探讨抑制单核细胞趋化蛋白-1（MCP-1）的表达是否可以用于抑制OSCC的骨侵袭。通过免疫组织化学 (IHC) 从 10 个 OSCC 档案块中观察到 MCP-1 蛋白的强染色。实时PCR显示MCP-1 mRNA在OSCC细胞系（SCC25、HN5和Tca8113）中高表达，其中SCC25细胞表达最高。使用载体 pcDNA 中截短 7 个氨基酸 (7ND) 的 MCP-1 显性失活变体的表达构建体转染 SCC25 细胞，并通过抗生素选择产生所得的稳定 SCC25 细胞 (SCC25-7ND)。与SCC25细胞的10％CM相比，SCC25-7ND细胞的10％条件培养基（CM，上清液）有效抑制由CD14（+）单核细胞亚群生长的人破骨细胞的形成。进一步将SCC25或SCC25-7ND细胞注射至裸鼠颅盖表面，建立OSCC骨侵袭动物模型。 H&E染色显示两组均形成分化良好的OSCC，肿瘤细胞侵入骨，破骨细胞位于典型的吸收陷窝内。 TRAP染色表明，与SCC25细胞相比，SCC25-7ND细胞的颅骨中发现的破骨细胞明显较少。这些数据证明了 MCP-1 与 OSCC 骨侵袭研究的相关性，并表明 MCP-1 作为抑制这种常见并发症的靶点的潜在价值。 (C) 2014 年 Wiley 期刊公司。
Bone invasion is a common complication of oral squamous cell carcinoma (OSCC), and this study sought to explore whether suppressed expression of monocyte chemotactic protein-1 (MCP-1) can be used to inhibit the bone invasion by OSCC. Strong staining of MCP-1 protein was observed from 10 archival blocks of OSCC by immunohistochemistry (IHC). Real-time PCR showed MCP-1 mRNA was highly expressed by OSCC cell lines (SCC25, HN5, and Tca8113), and SCC25 cells had the highest expression. An expression construct of a dominant negative variant of MCP-1 with 7 amino acids truncated (7ND), in the vector pcDNA was used to transfect SCC25 cells, and resultant stabilized SCC25 cells (SCC25-7ND) were generated by antibiotic selection. 10% conditioned media (CM, supernatant) of SCC25-7ND cells efficiently inhibited the formation of human osteoclasts grown from CD14(+) monocyte subpopulation, comparing with 10% CM of SCC25 cells. Further, cells of SCC25 or SCC25-7ND were injected onto the surface of calvariae of nude mice to establish an animal model of bone invasion by OSCC. H&E staining showed well-differentiated OSCC was formed in both groups, tumour cells invading the bone while osteoclasts locating in typical resorption lacunae. TRAP staining indicated significantly fewer osteoclasts were found in calvariae with cells of SCC25-7ND in comparison to cells of SCC25. These data demonstrate the relevance of MCP-1 with research on bone invasion by OSCC, and suggest the potential value of MCP-1 as a target to inhibit this common complication. (C) 2014 Wiley Periodicals, Inc.