Matrix Pore Size Governs Escape of Human Breast Cancer Cells from a Microtumor to an Empty Cavity

作者：Joe Tien, Usman Ghani, Yoseph W. Dance, Alex J. Seibel, M. Çağatay Karakan, K. L. Ekinci, Celeste M. Nelson · 发表于：iScience · 年份：2020 · DOI：10.1016/j.isci.2020.101673 · 被引用次数：50 · 研究领域：Cellular Mechanics and Interactions、Cancer Cells and Metastasis、3D Printing in Biomedical Research

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.