Mirza Sheefa, Jain Nayan, Rawal Rakesh
1 Department of Life Sciences, University School of Sciences, Gujarat University, Ahmedabad, India.
2 Division of Medicinal Chemistry and Pharmacogenomics, Department of Cancer Biology, The Gujarat Cancer & Research Institute, Ahmedabad, India.
Tumour Biol. 2017 Mar;39(3):1010428317695915. doi: 10.1177/1010428317695915.
Lung cancer stem cells are supposed to be the main drivers of tumor initiation, maintenance, drug resistance, and relapse of the disease. Hence, identification of the cellular and molecular aspects of these cells is a prerequisite for targeted therapy of lung cancer. Currently, analysis of circulating tumor cells has the potential to become the main diagnostic technique to monitor disease progression or therapeutic response as it is non-invasive. However, accurate detection of circulating tumor cells has remained a challenge, as epithelial cell markers used so far are not always trustworthy for detecting circulating tumor cells, especially during epithelial-mesenchymal transition. As cancer stem cells are the only culprit to initiate metastatic tumors, our aim was to isolate and characterize circulating tumor stem cells rather than circulating tumor cells from the peripheral blood of NSCLC adenocarcinoma as limited data are available addressing the gene expression profiling of lung cancer stem cells. Here, we reveal that CD44(+)/CD24(-) population in circulation not only exhibit stem cell-related genes but also possess epithelial-mesenchymal transition characteristics. In conclusion, the use of one or more cancer stem cell markers along with epithelial, mesenchymal and epithelial mesenchymal transition markers will prospectively provide the most precise assessment of the threat for recurrence and metastatic disease and has a great potential for forthcoming applications in harvesting circulating tumor stem cells and their downstream applications. Our results will aid in developing diagnostic and prognostic modalities and personalized treatment regimens like dendritic cell-based immunotherapy that can be utilized for targeting and eliminating circulating tumor stem cells, to significantly reduce the possibility of relapse and improve clinical outcomes.
肺癌干细胞被认为是肿瘤起始、维持、耐药及疾病复发的主要驱动因素。因此，识别这些细胞的细胞和分子特征是肺癌靶向治疗的先决条件。目前，循环肿瘤细胞分析因其非侵入性，有潜力成为监测疾病进展或治疗反应的主要诊断技术。然而，循环肿瘤细胞的准确检测仍然是一项挑战，因为迄今为止使用的上皮细胞标志物在检测循环肿瘤细胞时并不总是可靠的，尤其是在上皮-间质转化过程中。由于癌症干细胞是引发转移性肿瘤的唯一罪魁祸首，我们的目标是从非小细胞肺癌腺癌患者的外周血中分离并鉴定循环肿瘤干细胞而非循环肿瘤细胞，因为关于肺癌干细胞基因表达谱的可用数据有限。在此，我们发现循环中的CD44(+)/CD24(-)群体不仅表现出与干细胞相关的基因，还具有上皮-间质转化特征。总之，使用一种或多种癌症干细胞标志物以及上皮、间质和上皮-间质转化标志物，有望对复发和转移性疾病的威胁提供最精确的评估，并且在收获循环肿瘤干细胞及其下游应用方面具有巨大的应用潜力。我们的结果将有助于开发诊断和预后方法以及个性化治疗方案，如基于树突状细胞的免疫疗法，可用于靶向和消除循环肿瘤干细胞，以显著降低复发可能性并改善临床结果。
