Tien Joe, Ghani Usman, Dance Yoseph W, Seibel Alex J, Karakan M Çağatay, Ekinci Kamil L, Nelson Celeste M
Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Division of Materials Science and Engineering, Boston University, Boston, MA 02215, USA.
iScience. 2020 Oct 14;23(11):101673. doi: 10.1016/j.isci.2020.101673. eCollection 2020 Nov 20.
How the extracellular matrix (ECM) affects the progression of a localized tumor to invasion of the ECM and eventually to vascular dissemination remains unclear. Although many studies have examined the role of the ECM in early stages of tumor progression, few have considered the subsequent stages that culminate in intravasation. In the current study, we have developed a three-dimensional (3D) microfluidic culture system that captures the entire process of invasion from an engineered human micro-tumor of MDA-MB-231 breast cancer cells through a type I collagen matrix and escape into a lymphatic-like cavity. By varying the physical properties of the collagen, we have found that MDA-MB-231 tumor cells invade and escape faster in lower-density ECM. These effects are mediated by the ECM pore size, rather than by the elastic modulus or interstitial flow speed. Our results underscore the importance of ECM structure in the vascular escape of human breast cancer cells.
细胞外基质（ECM）如何影响局部肿瘤进展至侵入ECM并最终发生血管播散仍不清楚。尽管许多研究已探讨ECM在肿瘤进展早期阶段的作用，但很少有研究考虑到最终导致肿瘤细胞进入血管这一后续阶段。在本研究中，我们开发了一种三维（3D）微流控培养系统，该系统可捕捉MDA-MB-231乳腺癌细胞构成的工程化人类微肿瘤通过I型胶原基质侵入并逃逸至类淋巴腔的整个过程。通过改变胶原的物理特性，我们发现MDA-MB-231肿瘤细胞在低密度ECM中侵入和逃逸得更快。这些效应是由ECM孔径介导的，而非弹性模量或间质流速。我们的结果强调了ECM结构在人类乳腺癌细胞血管逃逸中的重要性。
