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

Joe Tien; Usman Ghani; Yoseph W Dance; Alex J Seibel; M Çağatay Karakan; Kamil L Ekinci; Celeste M Nelson

doi:10.1016/j.isci.2020.101673

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

iScience. 2020 Oct 14;23(11):101673. doi: 10.1016/j.isci.2020.101673. eCollection 2020 Nov 20.

Authors

Joe Tien^{1

2}, Usman Ghani¹, Yoseph W Dance¹, Alex J Seibel¹, M Çağatay Karakan^{3

4}, Kamil L Ekinci^{2

3

4}, Celeste M Nelson^{5

6}

Affiliations

¹ Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
² Division of Materials Science and Engineering, Boston University, Boston, MA 02215, USA.
³ Department of Mechanical Engineering, Boston University, Boston, MA 02215, USA.
⁴ Photonics Center, Boston University, Boston, MA 02215, USA.
⁵ Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08554, USA.
⁶ Department of Molecular Biology, Princeton University, Princeton, NJ 08554, USA.

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.

Keywords: Bioengineering; Biophysics; Cancer.

Abstract

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