Malara N M, Givigliano F, Trunzo V, Macrina L, Raso C, Amodio N, Aprigliano S, Minniti A M, Russo V, Roveda L, Coluccio M L, Fini M, Voci P, Prati U, Di Fabrizio E, Mollace V
Italian Institutes of Technology, Arnesano, Lecce, Italy.
Thoracic Surgery, Cancer Centre of Excellence, University Magna Graecia of Catanzaro, Italy.
J Biol Regul Homeost Agents. 2014 Oct-Dec;28(4):717-31.
The clinical development of locally and advanced non-small cell lung cancer (NSCLC) suffers from a lack of biomarkers as a guide in the selection of optimal prognostic prediction. Circulating Tumour Cells (CTCs) are correlated to prognosis and show efficacy in cancer monitoring in patients. However, their enumeration alone might be inadequate; it might also be critical to understand the viability, the apoptotic state and the kinetics of these cells. Here, we report what we believe to be a new and selective approach to visually detect tumour specific CTCs. Firstly, using labelled human lung cancer cells, we detected a specific density interval in which NSCL-CTCs were concentrated. Secondly, to better characterize CTCs in respect to their heterogeneous composition and tumour reference, blood and tumour biopsy were performed on specimens taken from the same patient. The approach consisted in comparing phenotype profile of CTCs, and their progenitor Tumour Stem Cells, (TSCs). Moreover, NSCL-CTCs were cultivated in short-time human cultures to provide response to drug sensitivity. Our bimodal approach allowed to reveal two items. Firstly, that one part of a tumour, proximal to the bronchial structure, displays a predominance of CD133+. Secondly, specific NSCL-CTCs Epithelial Cell Adhesion Molecule (EpCAM)+CD29+ can be used as a negative prognostic factor as well the high expression of CTCs EpCAM+. These data were confirmed by drug-sensitivity tests, in vitro, and by the survival curves, in vivo.
局部和晚期非小细胞肺癌（NSCLC）的临床发展缺乏生物标志物作为选择最佳预后预测的指导。循环肿瘤细胞（CTC）与预后相关，并在癌症患者监测中显示出有效性。然而，仅对其进行计数可能并不足够；了解这些细胞的活力、凋亡状态和动力学也可能至关重要。在此，我们报告了一种我们认为是视觉检测肿瘤特异性CTC的新的选择性方法。首先，使用标记的人肺癌细胞，我们检测到了NSCL-CTC集中的特定密度区间。其次，为了更好地根据其异质性组成和肿瘤参考来表征CTC，对来自同一患者的标本进行了血液和肿瘤活检。该方法包括比较CTC及其祖细胞肿瘤干细胞（TSC）的表型谱。此外，将NSCL-CTC在短期人类培养物中培养以提供对药物敏感性的反应。我们的双峰方法揭示了两点。首先，肿瘤靠近支气管结构的一部分显示出CD133+的优势。其次，特定的NSCL-CTC上皮细胞粘附分子（EpCAM）+CD29+可作为阴性预后因素以及CTC EpCAM+的高表达。这些数据在体外通过药物敏感性测试以及在体内通过生存曲线得到了证实。
