Insulin-like growth factor-II mRNA binding protein-3 and podoplanin expression are associated with bone invasion and prognosis in oral squamous cell carcinoma
Insulin-like growth factor-II mRNA binding protein-3 and podoplanin expression are associated with bone invasion and prognosis in oral squamous cell carcinoma
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DOI：
10.1016/j.archoralbio.2016.05.008
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发表时间：
2016-09-01
影响因子：
3
通讯作者：
Zhang, Xianglan
中科院分区：
文献类型：
--
作者：
Hwang, Young Sun;Ahn, Sung Yong;Zhang, Xianglan
目的：探讨胰岛素样生长因子-II mRNA结合蛋白-3(IMP3)和泊多普宁(PDPN)作为口腔鳞状细胞癌(OSCC)骨侵袭治疗靶点的预后意义。研究设计：探讨IMP3和PDPN在160例口腔鳞癌组织标本中的表达与骨侵袭的关系，并用IMP3和PDPN缺失的OSCC细胞系建立小鼠颅骨移植模型。结果：回顾性分析发现IMP3和PDPN的表达与口腔鳞癌患者的T分期、淋巴结转移和总生存期显著相关。此外，IMP3和PDPN的双重表达而不是IMP3和PDPN的单独表达与口腔鳞癌患者的骨侵袭和破骨细胞数量有关。为了支持这些发现，IMP3或PDPN的缺失抑制了口腔鳞状细胞癌细胞在三维培养系统中的侵袭能力，抑制了肿瘤的形成，并抑制了异种移植小鼠模型的局部骨破坏。此外，IMP3或PDPN的缺失抑制了口腔鳞癌细胞中IL-6和IL-8的表达，降低了OSCC移植瘤组织中核因子-kappaB受体激活剂配体(RANKL)的表达。结论：IMP3和PDPN可能在口腔鳞癌的发病机制中起重要作用，尤其是在骨侵袭方面，可作为预测骨侵袭性口腔鳞癌的新的治疗靶点。(C)2016爱思唯尔有限公司。保留所有权利。
Objective: This study aimed to evaluate the prognostic implications of insulin-like growth factor-II mRNA binding protein-3 (IMP3) and podoplanin (PDPN) as therapeutic targets against oral squamous cell carcinoma (OSCC) with bone invasion.Study design: We elucidated the correlation of IMP3 and PDPN expression with bone invasion in 160 OSCC tissue specimens, and assessed a mouse calvarium xenograft model using an IMP3- and PDPN-depleted OSCC cell line.Results: The retrospective analysis revealed that the expression of IMP3 and PDPN is significantly correlated with T stage, lymph node metastasis, and the overall survival of OSCC patients. In addition, the dual expression of IMP3 and PDPN but not the single expression of either IMP3 or PDPN was associated with bone invasion and the number of osteoclasts in patients with OSCC. In support of these findings, IMP3 or PDPN depletion inhibited the invasive capacity of OSCC cells in a three-dimensional culture system, tumorigenesis, and regional bone destruction in a xenograft mouse model. In addition, IMP3 or PDPN depletion inhibited the expression of interleukin (IL)-6 and IL-8 in OSCC cells, and decreased the expression of receptor activator of NF-kappa B ligand (RANKL) in xenograft tumor tissues of OSCC.Conclusions: These results suggest that IMP3 and PDPN may have strong influence on the pathogenesis of OSCC, especially in bone invasion, and may serve as novel therapeutic targets with prognostic implications for bone-invasive OSCC. (C) 2016 Elsevier Ltd. All rights reserved.