Microfluidic Mechanical-Separation Chips Identify Tumorigenic and Metastasis-Prone Breast Cells
“Our observations support the relationship between tumor-initiating capacity and cell deformability, and demonstrate that tumor-initiating cells are less differentiated in terms of cell biomechanics,” reported lead author Weijia Zhang, PhD, of the Department of Nanomedicine and Methodist Cancer Center, Methodist Hospital Research Institute, in Houston, TX, and coauthors from Cornell University and the MD Anderson Cancer Center's Morgan Welch Inflammatory Breast Cancer Research Program.
Put plainly, cancer-prone cells retain the “squishiness” of stem cells, the team found.
The researchers used microfluidic cell separation, gene-expression analysis and tumorigenicity assay to explore the relationship between cellular retention of stem cell-like deformability and metastatic potential. A microfluidic chip was used to separate a mixture of breast tumor cell types (MDA-MB-436 and MCF-7), each of which has different metastatic potentials. The team also tested the chip using a heterogeneous breast cancer cell line (SUM149) into flexible and inflexible populations, they reported.
“Driven by hydrodynamic forces, flexible cells or cells with high metastatic propensity change shape to pass through the micro-barriers, and exit the separation device, whereas stiff cells remain trapped,” Dr. Zhang explained.
The coauthors also report that the flexible-phenotype SUM149 cells have a gene-expression profile “indicative of greater cytoskeletal and nucleoskeletal deformability and motility” -- genes involved in cancer cell metastasis and “greater mammosphere formation efficiency,” they reported.
Several recent studies have shown that cancer stem cells or stem-like cells are associated with poor prognosis. The new method could allow rapid and inexpensive early assessment of anticancer therapies' efficacy for patients, or a newly-diagnosed cancer's metastatic potential. The microfluidic MS chips cost about $10 each to produce, and the authors anticipate that cost dropping to as little as $1 per chip.