Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Division of Hematology-Oncology, Penn State Hershey Cancer Institute; Hershey, PA, USA.
Cell Cycle. 2013 Jul 1;12(13):2132-43. doi: 10.4161/cc.25165. Epub 2013 Jun 11.
Cells disseminated from primary epithelial tumors into peripheral blood, called circulating tumor cells (CTCs), can be monitored to assess metastases and to provide a surrogate marker of treatment response. Here, we demonstrate how the flexible micro spring array (FMSA) device-a novel microfluidic device that enriches CTCs by two physical parameters: size and deformability-could be used in the rational development of treatment intervention and as a method to study the fundamental biology of CTCs. Cancer cells of different origins were spiked into healthy samples of donor blood to mimic blood samples of metastatic cancer patients. This spiked human blood was filtered using the FMSA device, and the recovered cells were successfully expanded in vitro and in a novel in vivo system. A series of experiments were performed to characterize these cells and to investigate the effect of chemotherapy on the resulting cultures. As few as 20 colon cancer cells in 7.5 mL blood could be isolated with the FMSA device, expanded both in vitro and in vivo and used at 25 cells per well to obtain significant and reliable chemosensitivity data. We also show that isolating a low number of viable patient CTCs and maintaining them in culture for a few weeks is possible. The isolation of viable cancer cells from human blood using the FMSA device provides a novel and realistic means for studying the biology of viable CTCs and for testing drug efficacy on these rare cells-a hypothesis that can be tested in future clinical trials.
从原发性上皮肿瘤扩散到外周血的细胞，称为循环肿瘤细胞 (CTC)，可以进行监测以评估转移并提供治疗反应的替代标志物。在这里，我们展示了柔性微弹簧阵列 (FMSA) 设备——一种通过两个物理参数（大小和变形性）富集 CTC 的新型微流控设备——如何用于治疗干预的合理开发以及作为研究 CTC 基本生物学的方法。将不同来源的癌细胞混入健康供体血液样本中，以模拟转移性癌症患者的血液样本。使用 FMSA 设备过滤这些加标人血，然后成功地在体外和新型体内系统中对回收的细胞进行了扩展。进行了一系列实验来对这些细胞进行表征，并研究化疗对所得培养物的影响。使用 FMSA 设备可以从 7.5 毫升血液中分离出多达 20 个结肠癌细胞，并且可以在体外和体内进行扩展，并以每个孔 25 个细胞的数量进行使用，以获得显著且可靠的化疗敏感性数据。我们还表明，从人血中分离出少量存活的患者 CTC 并在培养物中维持数周是可能的。使用 FMSA 设备从人血中分离出存活的癌细胞，为研究存活的 CTC 生物学和在这些稀有细胞上测试药物功效提供了一种新颖而现实的方法——这一假说可以在未来的临床试验中得到检验。
