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Issue 16, 2015
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A microengineered pathophysiological model of early-stage breast cancer

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Abstract

A mounting body of evidence in cancer research suggests that the local microenvironment of tumor cells has a profound influence on cancer progression and metastasis. In vitro studies on the tumor microenvironment and its pharmacological modulation, however, are often hampered by the technical challenges associated with creating physiological cell culture environments that integrate cancer cells with the key components of their native niche such as neighboring cells and extracellular matrix (ECM) to mimic complex microarchitecture of cancerous tissue. Using early-stage breast cancer as a model disease, here we describe a biomimetic microengineering strategy to reconstitute three-dimensional (3D) structural organization and microenvironment of breast tumors in human cell-based in vitro models. Specifically, we developed a microsystem that enabled co-culture of breast tumor spheroids with human mammary ductal epithelial cells and mammary fibroblasts in a compartmentalized 3D microfluidic device to replicate microarchitecture of breast ductal carcinoma in situ (DCIS). We also explored the potential of this breast cancer-on-a-chip system as a drug screening platform by evaluating the efficacy and toxicity of an anticancer drug (paclitaxel). Our microengineered disease model represents the first critical step towards recapitulating pathophysiological complexity of breast cancer, and may serve as an enabling tool to systematically examine the contribution of the breast cancer microenvironment to the progression of DCIS to an invasive form of the disease.

Graphical abstract: A microengineered pathophysiological model of early-stage breast cancer

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Article information


Submitted
06 May 2015
Accepted
02 Jul 2015
First published
09 Jul 2015

Lab Chip, 2015,15, 3350-3357
Article type
Paper
Author version available

A microengineered pathophysiological model of early-stage breast cancer

Y. Choi, E. Hyun, J. Seo, C. Blundell, H. C. Kim, E. Lee, S. H. Lee, A. Moon, W. K. Moon and D. Huh, Lab Chip, 2015, 15, 3350
DOI: 10.1039/C5LC00514K

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