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

TitleMatrix Pore Size Governs Escape of Human Breast Cancer Cells from a Microtumor to an Empty Cavity.
Publication TypeJournal Article
Year of Publication2020
AuthorsTien, J, Ghani, U, Dance, YW, Seibel, AJ, M Karakan, Ç, Ekinci, KL, Nelson, CM
JournaliScience
Volume23
Issue11
Pagination101673
Date Published2020 Nov 20
ISSN2589-0042
Abstract

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.

DOI10.1016/j.isci.2020.101673
Alternate JournaliScience
PubMed ID33163933
PubMed Central IDPMC7599434
Grant ListR01 CA187692 / CA / NCI NIH HHS / United States
T32 GM008764 / GM / NIGMS NIH HHS / United States
U01 CA214292 / CA / NCI NIH HHS / United States