Eslami Amirabadi H, SahebAli S, Frimat J P, Luttge R, den Toonder J M J
Microsystems Group, Department of Mechanical Engineering and Institute for Complex Molecular systems (ICMS), Eindhoven University of Technology, Groene Loper 15, 5612AZ, Eindhoven, the Netherlands.
Biomed Microdevices. 2017 Oct 17;19(4):92. doi: 10.1007/s10544-017-0234-8.
A major challenge in studying tumor cell invasion into its surrounding tissue is to identify the contribution of individual factors in the tumor microenvironment (TME) to the process. One of the important elements of the TME is the fibrous extracellular matrix (ECM) which is known to influence cancer cell invasion, but exactly how remains unclear. Therefore, there is a need for new models to unravel mechanisms behind the tumor-ECM interaction. In this article, we present a new microfabrication method, called selective curing, to integrate ECM-mimicking layers between two microfluidic channels. This method enables us to study the effect of 3D matrices with controlled architecture, beyond the conventionally used hydrogels, on cancer invasion in a controlled environment. As a proof of principle, we have integrated two electrospun Polycaprolactone (PCL) matrices with different fiber diameters in one chip. We then studied the 3D migration of MDA-MB-231 breast cancer cells into the matrices under the influence of a chemotactic gradient. The results show that neither the invasion distance nor the general cell morphology is affected significantly by the difference in fiber size of these matrices. The cells however do produce longer and more protrusions in the matrix with smaller fiber size. This microfluidic system enables us to study the influence of other factors in the TME on cancer development as well as other biological applications as it provides a controlled compartmentalized environment compatible with cell culturing.
研究肿瘤细胞侵入周围组织的一个主要挑战是确定肿瘤微环境（TME）中各个因素对这一过程的作用。TME的重要组成部分之一是纤维状细胞外基质（ECM），已知其会影响癌细胞的侵袭，但具体机制尚不清楚。因此，需要新的模型来揭示肿瘤与ECM相互作用背后的机制。在本文中，我们提出了一种新的微制造方法，称为选择性固化，用于在两个微流体通道之间整合模拟ECM的层。这种方法使我们能够在可控环境中研究具有可控结构的3D基质（超越传统使用的水凝胶）对癌症侵袭的影响。作为原理验证，我们在一个芯片中整合了两种不同纤维直径的电纺聚己内酯（PCL）基质。然后，我们研究了在趋化梯度影响下MDA-MB-231乳腺癌细胞向基质中的3D迁移。结果表明，这些基质的纤维尺寸差异对侵袭距离和一般细胞形态均无显著影响。然而，细胞在纤维尺寸较小的基质中确实会产生更长、更多的突起。这种微流体系统使我们能够研究TME中的其他因素对癌症发展的影响以及其他生物学应用,因为它提供了一个与细胞培养兼容的可控分隔环境。
