Quantification of cellular volume and sub-cellular density fluctuations: comparison of normal peripheral blood cells and circulating tumor cells identified in a breast cancer patient.
Quantification of cellular volume and sub-cellular density fluctuations: comparison of normal peripheral blood cells and circulating tumor cells identified in a breast cancer patient.
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DOI：
10.3389/fonc.2012.00096
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发表时间：
2012
影响因子：
4.7
通讯作者：
McCarty OJ
中科院分区：
文献类型：
--
作者：
Phillips KG;Kolatkar A;Rees KJ;Rigg R;Marrinucci D;Luttgen M;Bethel K;Kuhn P;McCarty OJ
癌症转移是癌症相关死亡的主要原因，在一定程度上是由循环肿瘤细胞（ctc）通过脉管系统的血运促进的。临床研究表明，ctc在主要类型的转移性癌症患者的血液中循环，并且外周血中ctc的数量与转移性乳腺癌、结直肠癌和前列腺癌的总生存率相关。虽然存在通过CTC计数监测转移的潜力，但CTC的基本物理特征仍然不明确，而且这些物理参数的相应临床用途尚不清楚。为了阐明ctc的基本物理特征，我们提出了一种无标记成像技术，利用差分干涉对比（DIC）显微镜来测量细胞体积，量化亚细胞质量密度变化以及亚细胞成分的大小。使用高清（HD） CTC检测法对乳腺癌患者中发现的CTC进行DIC测量。我们比较了HD-CTC与正常血细胞亚群的生物物理特征，包括白细胞、血小板（PLT）和红细胞（rbc）。与白细胞相比，hd - ctc具有更大的体积，更小的质量密度波动和更短的空间密度相关性。我们的研究结果表明，hd - ctc表现出生物物理特征，可能用于潜在地帮助检测它们并以无标签方式监测对治疗的反应。本文报道的生物物理参数可以纳入ctc -血管相互作用的计算模型和体外流动模型，以更好地了解转移。
Cancer metastasis, the leading cause of cancer-related deaths, is facilitated in part by the hematogenous transport of circulating tumor cells (CTCs) through the vasculature. Clinical studies have demonstrated that CTCs circulate in the blood of patients with metastatic disease across the major types of carcinomas, and that the number of CTCs in peripheral blood is correlated with overall survival in metastatic breast, colorectal, and prostate cancer. While the potential to monitor metastasis through CTC enumeration exists, the basic physical features of CTCs remain ill defined and moreover, the corresponding clinical utility of these physical parameters is unknown. To elucidate the basic physical features of CTCs we present a label-free imaging technique utilizing differential interference contrast (DIC) microscopy to measure cell volume and to quantify sub-cellular mass-density variations as well as the size of subcellular constituents from mass-density spatial correlations. DIC measurements were carried out on CTCs identified in a breast cancer patient using the high-definition (HD) CTC detection assay. We compared the biophysical features of HD-CTC to normal blood cell subpopulations including leukocytes, platelets (PLT), and red blood cells (RBCs). HD-CTCs were found to possess larger volumes, decreased mass-density fluctuations, and shorter-range spatial density correlations in comparison to leukocytes. Our results suggest that HD-CTCs exhibit biophysical signatures that might be used to potentially aid in their detection and to monitor responses to treatment in a label-free fashion. The biophysical parameters reported here can be incorporated into computational models of CTC-vascular interactions and in vitro flow models to better understand metastasis.