Metastasis of carcinomas (cancers that come from epithelial cells, which line organ surfaces) depends on cancer cells’ ability to travel from the tumor site and spread throughout the body, where the count of circulating tumor cells (CTCs) in the blood can be an indicator of metastatic risk.
The ability to accurately count the subset of CTCs that are most likely to metastasize could help clinicians better diagnose and treat cancer. Current methods of CTC detection only identify which cells have metastatic potential—a binary yes-or-no characterization.
In a new study published in the Journal of Chromatography A, researchers from the Department of Biomedical Engineering, led by Aaron Fleischman, PhD, and Maciej Zborowski, PhD, report on a new device they’ve developed to identify and perform differential counts of CTCs, which their findings suggest may be more accurate and help to better assess cancer metastasis risk.
Improving the enumeration process
Currently, researchers identify CTCs in the blood using magnetic nanoparticles that specifically bind to molecules called epithelial cell adhesion molecules (EpCAMs). EpCAMs are found only on epithelial cells (but not nucleated, white blood cells), and are a marker for carcinoma. When exposed to the magnetic device, all cells that express any EpCAMs are drawn to the magnet and can be isolated for counting.
Here, the researchers developed a device that is more sensitive and can measure metastatic potential on a gradient of the magnetic field—in that way better reflecting the fact that CTCs are a heterogeneous class of cells and likely contribute to disease in a complex way. Drs. Fleischman’s and Zborowski’s device, called the dipole magnetic fractionator (DMF), uses the same nanoparticle system, but attracts cells based on the amount of EpCAMs they express.
The DMF is a chamber that has three inlets and six outlets and a magnetic field that spans the top. In a simulation of the device, the researchers found that CTCs that are more likely to metastasize (those with the greatest expression of EpCAMs) were drawn upward, closest to the magnet, and those with the least EpCAM expression settled nearer to the bottom of the chamber.
An easier way to monitor cancer progression
This method of assessing metastasis risk—a “liquid biopsy”—would be more convenient for the patient and the clinician.
“Because blood is the main way that CTCs are disseminated, the ability to detect these cells represents a useful and readily available tool,” Dr. Fleischman noted. “CTC detection may give clinicians the opportunity to detect metastatic cancer early in the process, which would enable them to better screen and detect relapse earlier, and could help inform personalized treatment approaches.”
According to Dr. Zborowski, the level of detail and convenience afforded by this device make this approach superior to previous devices.
“We have refined the cell separators by innovative engineering of the gradated magnetic field and matching microfluidics for magnetic, graduated CTC separation, according to the level of their EpCAM marker expression,” he said. “This represents their metastatic potential better than a simple yes-or-no answer possible with the current magnetic cell separation methods.”
Adds Dr. Fleischman, “This device will be beneficial to both clinical oncologists, who will be able to easily gauge metastatic risk, and to research oncologists, who will be able to conduct studies of pure CTC subpopulations that correlate with metastatic disease and drug resistance.”
This study was supported by the National Institutes of Health and the U.S. National Science Foundation.