Translational Radiooncology and Radiobiology Research Laboratory, Department of Radiooncology and Radiotherapy.
Int J Radiat Biol. 2014 Aug;90(8):622-7. doi: 10.3109/09553002.2014.886798. Epub 2014 May 12.
To review the results from previous studies aiming at the molecular characterization of circulating tumor cells (CTC), to specifically address the role of epithelial-mesenchymal-transition (EMT) and stemness features of CTC in their contribution to tumor progression and to summarize potential interference of CTC with the efficacy of radiotherapy.
Detection of CTC has been reported for most epithelial tumors and has been associated with an increased risk of local and regional recurrence as well as the development of distant metastases. Given a causal relationship between the presence of CTC and tumor progression at the primary or distant sites, several distinct features have to be postulated for these cells: First, a change from an epithelial to a mesenchymal cell-like phenotype which should alleviate the disconnection of individual tumor cells from tight cell-to-cell junctions within the epithelial cell layer and endow single tumor cells with the capacity to migrate into blood vessels; secondly, the presence of stem-cell properties which contribute to the re-establishment of bulk tumor tissue at the primary or metastatic site upon tumor recurrence or distant progression, respectively. Indeed, EMT and stem-cell features were frequently observed in CTC and the phenotype of CTC was established as a stronger predictor of outcome than sole enumeration of CTC in a defined volume of blood. The exploitation of CTC above their use as prognostic marker is still a subject of many ongoing investigations as are the identification of suitable therapeutic targets for this small cell subpopulation.
回顾先前研究的结果,旨在对循环肿瘤细胞(CTC)进行分子特征分析,特别关注上皮-间质转化(EMT)和 CTC 的干性特征在促进肿瘤进展中的作用,并总结 CTC 对放疗效果的潜在干扰。
大多数上皮肿瘤都有 CTC 的检测报道,并与局部和区域复发以及远处转移的风险增加相关。鉴于 CTC 的存在与原发性或远处部位的肿瘤进展之间存在因果关系,必须为这些细胞提出几个不同的特征:首先,从上皮样细胞样表型转变为间充质细胞样表型,这应该减轻单个肿瘤细胞与其在上皮细胞层中紧密细胞-细胞连接的分离,并赋予单个肿瘤细胞迁移到血管中的能力;其次,存在干细胞特性,这有助于在肿瘤复发或远处进展时在原发性或转移性部位重新建立肿瘤组织。事实上,EMT 和干细胞特征经常在 CTC 中观察到,并且 CTC 的表型被确立为比在特定体积的血液中单纯计数 CTC 更能预测结果的指标。对 CTC 的利用不仅限于作为预后标志物,这仍然是许多正在进行的研究的主题,也是确定针对这个小细胞亚群的合适治疗靶点的主题。