Molecular analysis of anoikis resistance in oral cavity squamous cell carcinoma
Molecular analysis of anoikis resistance in oral cavity squamous cell carcinoma
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DOI：
10.1016/j.oraloncology.2006.04.016
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发表时间：
2007-05-01
期刊：
影响因子：
4.8
通讯作者：
Myers, Jeffrey N.
中科院分区：
文献类型：
--
作者：
Kupferman, Michael E.;Patel, Vyomesh;Myers, Jeffrey N.
口腔鳞状细胞癌（Oral cavity squamous cell carcinoma，OSCC）是世界范围内癌症死亡的主要原因之一，并且这些死亡大多数是由局部区域复发和转移引起的。凋亡的逃避是癌症发展和进展的重要标志，并且先前的研究已经表明，逃避失巢凋亡或凋亡诱导的凋亡与OSCC中癌细胞的更具侵袭性的表型相关。为了阐明抗失巢凋亡的细胞遗传学和分子特征，我们产生了几个显示这种细胞表型的细胞系和克隆。为了验证染色体改变可能是这种表型转化的基础这一假设，我们使用核型分析来观察失巢凋亡敏感和抗失巢凋亡细胞系的染色体结构变化。我们进一步假设，一个独特的模式的基因表达诱导细胞脱落的失巢凋亡抗性细胞系，和cDNA微阵列分析进行了使用面板的失巢凋亡抗性口腔癌细胞系生长在附着和分离的生长条件下。我们确定了S100 P，KLK 6和CTNNAL 1作为基因，其表达水平在脱落条件下的失巢凋亡抵抗细胞与失巢凋亡敏感细胞相比差异调节。这些结果用实时RT-PCR进行了验证。鳞状细胞癌的抗失巢凋亡表型具有独特的遗传表达模式，其特征在于染色体改变，这可能有助于参与不同细胞功能的基因的差异表达。靶向这些失巢凋亡抵抗的潜在介质的疗法可能被证明在转移性鳞状细胞癌的治疗中是有益的。(c)2006爱思唯尔有限公司保留所有权利。
Oral cavity squamous cell carcinoma (OSCC) is one of the leading causes of cancer deaths worldwide and most of these deaths result from local-regional recurrence and metastases. Evasion of apoptosis is an important hallmark of cancer development and progression, and previous studies have shown that evasion of anoikis, or detachment-induced apoptosis, correlates with a more aggressive phenotype of carcinoma cells in OSCC. To elucidate the cytogenetic and molecular characteristics of anoikis resistance, we generated several cell lines and clones that displayed this cellular phenotype. To test the hypothesis that chromosomal alterations may underlie this phenotypic transformation, we used karyotype analysis to observe changes in the chromosomal structure of anoikis-sensitive and anoikis-resistant cell tines. We further hypothesized that a unique pattern of gene expression was induced by cell-detachment of anoikis-resistant cell lines, and cDNA microarray analysis was performed using a panel of anoikis-resistant oral cancer cell lines grown under attached and detached growth conditions. We identified S100P, KLK6 and CTNNAL1 as genes whose expression levels were differentially regulated in the anoikis-resistant cell tines compared to the anoikis-sensitive cells under detached conditions. These results were verified using real-time RT-PCR. The anoikis-resistant phenotype of squamous cell carcinoma has a distinct genetic expression pattern that is marked by chromosomal alterations that may contribute to differential expression of genes involved in diverse cellular functions. Therapies targeting these potential mediators of anoikis resistance may prove to be beneficial in the treatment of metastatic squamous cell carcinoma. (c) 2006 Elsevier Ltd. All rights reserved.