Department of Biotechnology, Yonsei University, Seoul, Korea.
Lab Chip. 2011 Nov 21;11(22):3880-7. doi: 10.1039/c1lc20671k. Epub 2011 Oct 5.
Most studies of cancer metastasis focus on cancer cell invasion utilizing adhesion assays that are performed independently, and are thus limited in their ability to mimic complex cancer metastasis on a chip. Here we report the development of an integrated cell-based microfluidic chip for intra- and extravasation that combines two assays on one chip for the study of the complex cascade of cancer metastasis. This device consists of two parts; one is an intravasation chamber for the three-dimensional (3-D) culture of cancer cells using a Matrigel matrix, and the other is an extravasation chamber for the detection of metastasized cancer cells by adhesion molecules expressed by epithelial cells. In this novel system, the intravasation and extravasation processes of cancer metastasis can be studied simultaneously using four screw valves. Metastatic LOVO and non-metastatic SW480 cells were used in this study, and the invasion of LOVOs was found to be higher compared to SW480. In contrast, invasion of cells treated with metalloproteinase (MMP) inhibitors decreased within the intravasation chamber. Degraded cancer cells from the intravasation chamber were detected within the extravasation chamber under physiological conditions of shear stress, and differences in binding efficiency were also detected when CA19-9 antibody, an inhibitor of cancer cell adhesion, was used to treat degraded cancer cells. Our results support the potential usefulness of this new 3D cell-based microfluidic system as a drug screening tool to select targets for the development of new drugs and to verify their effectiveness.
大多数癌症转移的研究都集中在利用粘附测定法研究癌细胞侵袭上，这些测定法是独立进行的，因此在模拟芯片上复杂的癌症转移方面能力有限。在这里，我们报告了一种用于细胞内和细胞外渗的集成基于细胞的微流控芯片的开发，该芯片将两种测定法结合在一个芯片上，用于研究癌症转移的复杂级联。该装置由两部分组成；一部分是用于使用基质胶进行三维（3-D）培养癌细胞的血管内渗室，另一部分是用于通过上皮细胞表达的粘附分子检测转移癌细胞的血管外渗室。在这个新系统中，使用四个螺丝阀可以同时研究癌症转移的血管内渗和血管外渗过程。在这项研究中使用了转移性 LOVO 和非转移性 SW480 细胞，发现 LOVO 的侵袭性高于 SW480。相比之下，在血管内渗室中用金属蛋白酶（MMP）抑制剂处理的细胞侵袭性降低。在生理剪切应力条件下，从血管内渗室中检测到降解的癌细胞进入血管外渗室，并且当使用 CA19-9 抗体（一种抑制癌细胞黏附的抑制剂）处理降解的癌细胞时，还检测到结合效率的差异。我们的结果支持这种新的 3D 基于细胞的微流控系统作为药物筛选工具的潜在有用性，以选择开发新药的靶点并验证其有效性。
