Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression
Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression
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DOI：
10.3390/cancers6010128
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发表时间：
2014-03-01
期刊：
影响因子：
5.2
通讯作者：
Galanzha, Ekaterina I.
中科院分区：
文献类型：
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作者：
Juratli, Mazen A.;Sarimollaoglu, Mustafa;Galanzha, Ekaterina I.
循环肿瘤细胞（CTCs）是一种很有前景的转移性肿瘤诊断和预后生物标志物。通过对CTC动态的实时监测，可以提高CTC的诊断价值。利用乳腺癌和黑色素瘤的临床前动物模型以及体内光声和荧光检测原理图的流式细胞术，我们发现CTC计数并不总是与原发肿瘤大小相关。个体分析阐明了许多在原发肿瘤开始进展之前检测到最高水平ctc的病例。这种现象可能是由癌症干细胞发展而来的侵袭性肿瘤。此外，对CTCs的实时连续监测表明，在一段时间内，它们在一个检测点以高度可变的速率发生（例如，每5分钟0-54个CTCs）。在体内，在上皮性和非上皮性转移性肿瘤、肿瘤进展的不同阶段和不同血管中，观察到CTC数量的相同波动。这些暂时的CTC波动可以解释人类一次性快照测试的假阴性结果。事实上，我们观察到，在同一转移性黑色素瘤患者的后续血液样本中，ctc的数量存在很大差异，其中一些样本不含ctc。如果这些现象在我们正在进行的体内临床试验中得到证实，这将为癌症患者的CTC监测个性化策略提供支持。
Circulating tumor cells (CTCs) are a promising diagnostic and prognostic biomarker for metastatic tumors. We demonstrate that CTCs' diagnostic value might be increased through real-time monitoring of CTC dynamics. Using preclinical animal models of breast cancer and melanoma and in vivo flow cytometry with photoacoustic and fluorescence detection schematics, we show that CTC count does not always correlate with the primary tumor size. Individual analysis elucidated many cases where the highest level of CTCs was detected before the primary tumor starts progressing. This phenomenon could be attributed to aggressive tumors developing from cancer stem cells. Furthermore, real-time continuous monitoring of CTCs reveals that they occur at highly variable rates in a detection point over a period of time (e. g., a range of 0-54 CTCs per 5 min). These same fluctuations in CTC numbers were observed in vivo in epithelial and non-epithelial metastatic tumors, in different stages of tumor progression, and in different vessels. These temporal CTC fluctuations can explain false negative results of a one-time snapshot test in humans. Indeed, we observed wide variations in the number of CTCs in subsequent blood samples taken from the same metastatic melanoma patient, with some samples being CTC-free. If these phenomena are confirmed in our ongoing in vivo clinical trials, this could support a personalized strategy of CTC monitoring for cancer patients.