May 22, 2006
Microfluidics Device Tracks Breast Cancer Cell Movements
Malignant cells are notorious for their ability to break away from a tumor, migrate to other seemingly targeted locations in the body, and establish new tumors, called metastases. The biochemical signals that guide tumor cell migration are poorly understood, but efforts to find those signals should receive a boost thanks to a new microfluidics device designed specifically to track how breast cancer cells move in response to chemical signals.
Reporting its work in the journal Biomedical Microdevices, a research team led by Noo Li Jeon, Ph.D., at the University of California, Irvine, describes its efforts to use microfluidics to study cancer cell mobility, particularly in response to chemical signals that might be produced and released into the bloodstream by cells distant from an initial tumor. The investigators focused on creating a device that would create well-defined gradients of growth factors through which individual cells could move as they might when sensing different amounts of these chemical signals in their native environment. The researchers also wanted their device to have the ability to track simultaneously many different cells, responding to a variety of conditions.
To build such a device, the investigators created a microfluidic chamber with multiple inlets that can be programmed to dispense different concentrations of growth factor. The net effect of having multiple inlets is that it is possible to produce virtually any gradient across the chamber. To demonstrate the utility of this device, the researchers studied how breast cancer cells responded to gradients of epidermal growth factor (EGF). Newly growing blood vessels release EGF and many cancer researchers believe that this chemical signal plays a role in triggering the early stages of metastasis.
The set of experiments with EGF showed that breast cancer cells are strongly attracted to EFG and will migrate in a pattern that depends on shape of the gradient created in the tracking chamber. A sharp gradient, that is one in which the concentration of EGF drops sharply across the chamber, triggers rapid movement toward the highest concentration of EGF. In contrast, a shallow gradient, in which the concentration of EGF drops gradually across the chamber, triggers a more moderate response that only causes some of the cells to migrate toward higher concentration of EGF while others continue taking a more random path through the chamber.
The investigators also found that adding an anti-EGF antibody to the gradient blocked purposeful cell migration, that is, breast cancer cells would move through the chamber in a random manner. Based on this observation, the researchers concluded that a cancer cell responds to EGF by changing both the speed and direction of its migration, but that other growth factors may be triggering the initial metastatic signals that cause cancer cells to first become mobile. The investigators suggest that this device could be used to better categorize the different responses of cancer cells to potential inhibitors of metastasis, and thereby develop therapeutic agents designed specifically to block cancer cell metastasis while leaving normal cell migration unaffected.
This work is detailed in a paper titled, “A parallel-gradient microfluidic chamber for quantitative analysis of breast cancer cell chemotaxis.” An abstract of this paper is available through PubMed.