Epithelial cell translocation: new insights into mechanisms of tumor initiation.
Epithelial cell translocation: new insights into mechanisms of tumor initiation.
复制标题
DOI：
10.1002/bies.201200151
复制
发表时间：
2013-02
期刊：
影响因子：
4
通讯作者：
Leung, Cheuk T.
中科院分区：
文献类型：
--
作者：
Leung, Cheuk T.
肿瘤发展是一种克隆进化过程，起源于正常组织（如上皮）内出现的散发性突变细胞[1]。肿瘤的发生，即从组织学正常组织开始的肿瘤生长过程，是肿瘤发展级联反应的早期里程碑。这些突变细胞的存活和扩增促进了进一步致癌改变的积累，从而增强肿瘤的发展。尽管它在肿瘤进化层次中的重要性，但对肿瘤发生的机制知之甚少，我们对肿瘤发生的大部分知识都是从培养中的实验性细胞转化和动物模型中癌基因过表达或肿瘤抑制基因敲除驱动的肿瘤形成的遗传学研究中推断出来的，通常经过数周至数月的长潜伏期。虽然信息丰富，但这些模型不适合解决细胞事件的级联反应，通过该级联反应，散发性突变细胞在天然组织环境中进化。虽然遗传改变是肿瘤发生的基本驱动因素，但许多证据表明，组织环境可以极大地影响细胞行为，从而影响肿瘤的发展。鸡胚胎和小鸡的经典研究表明，正常组织环境可以抑制劳斯肉瘤病毒的细胞转化[2，3]。临床观察还表明，已知驱动肿瘤进展的致癌改变有时在组织学正常上皮组织内的细胞中发现[4，5]。这些数据表明，从完整组织中的休眠突变细胞到肿瘤生长的进展是肿瘤起始的关键步骤。
Tumor development is a clonal evolution process originating from sporadic mutant cells that arise within a normal tissue, such as an epithelium [1]. Tumor initiation, the processes that contribute to the initial neoplastic outgrowth from histologically normal tissues, represents an early milestone in the cascade of tumor evolution. Survival and expansion of these founding mutant cells facilitates the accumulation of further oncogenic alterations that potentiate tumor development. Despite its importance in the tumor evolution hierarchy, very little is known about the mechanisms that underlie tumor initiation.Much of our knowledge of tumor initiation is inferred from experimental cell transformation in culture and genetic studies of tumor formation driven by oncogene overexpression or tumor suppressor knockdown in animal models, usually after a long latency of weeks to months. While informative, these models are not amenable to address the cascade of cellular events through which sporadic mutant cells evolve within the native tissue environment. Although genetic alterations are the basic drivers of tumorigenesis, many lines of evidence suggest that the tissue environment can greatly influence cell behavior and, thus, tumor development. Classic studies in chicken embryos and young chickens have demonstrated that normal tissue environment can suppress cell transformation by the Rous sarcoma virus [2, 3]. Clinical observations have also indicated that oncogenic alterations known to drive tumor progression are sometimes found in cells within histologically normal epithelial tissues [4, 5]. These data suggest that the advancement from dormant mutant cells in intact tissues to neoplastic outgrowth is a critical step of tumor initiation.
登录
查看更多内容
影响因子：
64.5
作者：
Moreno, E;Basler, K
通讯作者：
Basler, K
影响因子：
56.9
作者：
Shen, J;Dahmann, C
通讯作者：
Dahmann, C
影响因子：
5.6
作者：
Underwood, Jean M.;Imbalzano, Karen M.;Nickerson, Jeffrey A.
通讯作者：
Nickerson, Jeffrey A.
影响因子：
64.8
作者：
DOLBERG, DS;BISSELL, MJ
通讯作者：
BISSELL, MJ
影响因子：
64.5
作者：
Li, Wei;Baker, Nicholas E.
通讯作者：
Baker, Nicholas E.