Correlation of NF-kappaB signal pathway with tumor metastasis of human head and neck squamous cell carcinoma.
Correlation of NF-kappaB signal pathway with tumor metastasis of human head and neck squamous cell carcinoma.
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DOI：
10.1186/1471-2407-10-437
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发表时间：
2010-08-17
期刊：
影响因子：
3.8
通讯作者：
Chen WT
中科院分区：
文献类型：
--
作者：
Yan M;Xu Q;Zhang P;Zhou XJ;Zhang ZY;Chen WT
核因子κB （NF-κB）信号在多种癌症发生、发展和治疗的多步骤过程中起着关键作用。然而，NF-κB通路在头颈癌进展的复杂和组织特异性方面的意义，如侵袭和转移，尚不清楚。免疫组化法研究NF-κB p65在头颈部鳞状细胞癌（SCCHN）临床标本中的表达采用western blot法、报告基因法、EMSA法对不同转移潜力肿瘤细胞进行体外和体内转移试验，探讨NF-κB活性在头颈部鳞状细胞癌中的作用。Annexin V/PI染色和Western blot分别检测转移相关蛋白MMP9和VEGF的凋亡率和表达。转移性SCCHN标本组活性核定位NF-κB水平较高（p < 0.01）。然后测定了具有不同转移潜力的SCCHN细胞系的NF-κB活性，结果与SCCHN标本的结果非常一致，高转移的SCCHN细胞系表达高水平的NF-κB活性。用NF-κB抑制剂治疗高转移性SCCHN细胞，可降低细胞的体外细胞侵袭能力，但不影响细胞凋亡率。此外，NF-κB抑制剂显著抑制裸鼠Tb细胞的肺转移和TL细胞的淋巴结转移。此外，吡咯烷二硫代碳酸酯可抑制转移相关蛋白如基质金属蛋白酶9和血管内皮生长因子的表达。该研究表明，NF-κB活性显著促进肿瘤血液和淋巴转移，并可能有助于开发针对非常规分子靶点的早期检测方法或治疗方法。
Nuclear factor-kappa B (NF-κB) signaling constitutes a key event in the multistep process of carcinogenesis, progression and treatment in many cancer types. However, the significance of NF-κB pathway for complex and tissue-specific aspects of head and neck cancer progression, such as invasion and metastasis, is less understood. The expression of NF-κB p65 in squamous cell carcinoma of the head and neck (SCCHN) clinical specimens by immunohistochemistry. The role of NF-κB activity in head and neck squamous cell carcinoma was determined by western blot, reporter assay and EMSA analysis in vitro and metastasis assays in vivo in different metastatic potential tumor cells. Furthermore, the apoptosis rate and expression of metastasis-related protein such as MMP9 and VEGF were examined by Annexin V/PI staining and Western blot, respectively. A higher level of active nuclear-localized NF-κB was observed in the metastatic SCCHN specimens group (p < 0.01). The NF-κB activities of SCCHN cell lines with different metastatic potentials were then determined and in excellent agreement with results found in SCCHN specimens, highly metastatic SCCHN cell lines expressed high level of NF-κB activity. The treatment of highly metastatic SCCHN cells with NF-κB inhibitors reduced the in vitro cell invasion capacity of the cells without affecting the apoptotic rate. Additionally, the NF-κB inhibitors significantly inhibited the experimental lung metastasis of Tb cells and lymph node metastasis of TL cells in nude mice. Furthermore, the expression of metastasis-related proteins, such as matrix metalloproteinase 9 and vascular endothelial growth factor, was inhibited by pyrrolidine dithiocarbonate. This study suggests that NF-κB activity significantly contributes to tumor hematologic and lymphatic metastases and may aid in the development of early detection methods or therapies targeting non-conventional molecular targets.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
分子对肿瘤细胞缺氧的反应。
影响因子：
37.3
作者：
Kunz, Manfred;Ibrahim, Saleh M
通讯作者：
Ibrahim, Saleh M
影响因子：
82.9
作者：
Park, Bae Keun;Zhang, Honglai;Wang, Cun-Yu
通讯作者：
Wang, Cun-Yu
DOI：
10.1158/1078-0432.ccr-09-1352
发表时间：
2009-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Arun P;Brown MS;Ehsanian R;Chen Z;Van Waes C
通讯作者：
Van Waes C
影响因子：
4.8
作者：
Helbig, G;Christopherson, KW;Nakshatri, H
通讯作者：
Nakshatri, H