Breast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment
Author(s)
Truong, Danh; Puleo, Julieann; Llave, Alison; Mouneimne, Ghassan; Nikkhah, Mehdi; Kamm, Roger Dale; ... Show more Show less
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In this study, to model 3D chemotactic tumor-stroma invasion in vitro, we developed an innovative microfluidic chip allowing side-by-side positioning of 3D hydrogel-based matrices. We were able to (1) create a dual matrix architecture that extended in a continuous manner, thus allowing invasion from one 3D matrix to another, and (2) establish distinct regions of tumor and stroma cell/ECM compositions, with a clearly demarcated tumor invasion front, thus allowing us to quantitatively analyze progression of cancer cells into the stroma at a tissue or single-cell level. We showed significantly enhanced cancer cell invasion in response to a transient gradient of epidermal growth factor (EGF). 3D tracking at the single-cell level displayed increased migration speed and persistence. Subsequently, we analyzed changes in expression of EGF receptors, cell aspect ratio, and protrusive activity. These findings show the unique ability of our model to quantitatively analyze 3D chemotactic invasion, both globally by tracking the progression of the invasion front, and at the single-cell level by examining changes in cellular behavior and morphology using high-resolution imaging. Taken together, we have shown a novel model recapitulating 3D tumor-stroma interactions for studies of real-time cell invasion and morphological changes within a single platform.
Date issued
2016-09Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Mechanical EngineeringJournal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Truong, Danh; Puleo, Julieann; Llave, Alison; Mouneimne, Ghassan; Kamm, Roger D. and Nikkhah, Mehdi. “Breast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment.” Scientific Reports 6, no. 1 (September 2016): 34094_1 - 34094_18 © 2016 Macmillan Publishers Limited, part of Springer Nature
Version: Final published version
ISSN
2045-2322