Subtype-specific characterization of breast cancer invasion using a microfluidic tumor platform

Abstract

Understanding progression of breast cancers to invasive ductal carcinoma (IDC) can significantly improve breast cancer treatments. However, it is still difficult to identify genetic signatures and the role of tumor microenvironment to distinguish pathological stages of preinvasive lesion and IDC. Presence of multiple subtypes of breast cancers makes the assessment more challenging. In this study, an in-vitro microfluidic assay was developed to quantitatively assess the subtype-specific invasion potential of breast cancers. The developed assay is a microfluidic platform in which a ductal structure of epithelial cancer cells is surrounded with a three-dimensional (3D) collagen matrix. In the developed platform, two triple negative cancer subtypes (MDA-MB-231 and SUM-159PT) invaded into the surrounding matrix but the luminal A subtype, MCF-7, did not. Among invasive subtypes, SUM-159PT cells showed significantly higher invasion and degradation of the surrounding matrix than MDA-MB-231. Interestingly, the cells cultured on the platform expressed higher levels of CD24 than in their conventional 2D cultures. This microfluidic platform may be a useful tool to characterize and predict invasive potential of breast cancer subtypes or patient-derived cells.

The Role of Functionalization and Size of Gold Nanoparticles in the Response of MCF-7 Breast Cancer Cells to Ionizing Radiation Comparing 2D and 3D In Vitro Models

“…For the experiments, the MCF-7 breast cancer cell line was used. This cell line is characterized by the Luminal A subtype expressing estrogen receptor (ER) and progesterone receptor (PR) [ 15 ]. The luminal-A is the most common subtype and represents 50–60% of all breast cancers [ 16 ].…”

Biomedical Applications of Microfluidic Devices: A Review

“…The studies on microfluidic cell culture technology in the literature pointed out different aspects of cancer modeling, including cancer cell invasion [ 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 ], intravasation [ 284 , 285 ], extravasation [ 286 , 287 , 288 ], and tumor microenvironment modeling [ 289 , 290 ]. Cell invasion refers to cell motility, including attachment, proteolysis, and relocation of cancer cells, which may result in cancer metastasis [ 291 ].…”

Cancer-on-a-Chip: Models for Studying Metastasis

“…Using a vascularized microfluidic chip, it was shown that MDA-MB-231 breast cancer cells invaded paracellularly by disrupting the endothelial junction, whereas HepG2 liver cancer cells invaded through the transcellular process [29]. Using another in vitro model of an invasive ductal carcinoma (IDC)-on-a-chip model that was developed using viscous fingering method, invasive characteristics of different human breast cancer cell lines were identified [30]. Breast cancers have been classified into different subtypes by their different gene expression profiles, which include luminal A, luminal B, hormone epidermal growth factor receptor 2 (HER-2) enriched, basal-like, and triplenegative breast cancer (TNBC) type.…”