E-cadherin is a cell-cell adhesion protein that plays a prominent role in cancer invasion. Inactivation of E-cadherin in breast cancer can arise from gene promoter hypermethylation or genetic mutation. Depending on their E-cadherin status, breast cancer cells adopt different morphologies with distinct invasion modes. The tumor microenvironment (TME) can also affect the cell morphology and invasion mode. In this paper, we used a previously developed microfluidic system to quantify the three-dimensional invasion of breast cancer cells with different E-cadherin status, namely MCF-7, CAMA-1 and MDA-MB-231 with wild type, mutated and promoter hypermethylated E-cadherin, respectively. The cells migrated into a stable and reproducible microfibrous polycaprolactone mesh in the chip under a programmed stable chemotactic gradient. We observed that the MDA-MB-231 cells invaded the most, as single cells. MCF-7 cells collectively invaded into the matrix more than CAMA-1 cells, maintaining their E-cadherin expression. The CAMA-1 cells exhibited multicellular multifocal infiltration into the matrix. These results are consistent with what is seen in vivo in the cancer biology literature. In addition, comparison between complete serum and serum gradient conditions showed that the MDA-MB-231 cells invaded more under the serum gradient after one day, however this behavior was inverted after 3 days. The results showcase that the microfluidic system can be used to quantitatively assess the invasion behavior of cancer cells with different E-cadherin expression, for a longer period than conventional invasion models. In the future, it can be used to quantitatively investigate effects of matrix structure and cell treatments on cancer invasion.

中文翻译：

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使用微流体系统在 3D 中表征具有不同 E-钙粘蛋白状态的不同乳腺癌细胞系的侵袭。


E-钙粘蛋白是一种细胞间粘附蛋白，在癌症侵袭中发挥着重要作用。乳腺癌中E-钙粘蛋白的失活可能是由基因启动子高甲基化或基因突变引起的。根据其E-钙粘蛋白状态，乳腺癌细胞采用不同的形态和不同的侵袭模式。肿瘤微环境（TME）也会影响细胞形态和侵袭模式。在本文中，我们使用先前开发的微流体系统来量化具有不同E-cadherin状态的乳腺癌细胞的三维侵袭，即野生型、突变型和启动子型的MCF-7、CAMA-1和MDA-MB-231分别是高甲基化的E-钙粘蛋白。在编程的稳定趋化梯度下，细胞迁移到芯片中稳定且可重复的微纤维聚己内酯网中。我们观察到 MDA-MB-231 细胞作为单细胞侵袭最多。 MCF-7 细胞比 CAMA-1 细胞更多地侵入基质，维持其 E-钙粘蛋白表达。 CAMA-1 细胞表现出多细胞多灶性浸润到基质中。这些结果与癌症生物学文献中在体内看到的结果一致。此外，完全血清和血清梯度条件之间的比较表明，一天后MDA-MB-231细胞在血清梯度下侵袭更多，但这种行为在3天后逆转。结果表明，微流控系统可用于定量评估具有不同E-cadherin表达的癌细胞的侵袭行为，比传统侵袭模型的持续时间更长。 未来可用于定量研究基质结构和细胞治疗对癌症侵袭的影响。