Web Date: November 19, 2012
Listening To Cancer Cells Chat
Cells within tumors must communicate with each other to coordinate their growth. Cancer researchers want to understand the cells’ language so they can disrupt the communication and shrink the tumors. Now researchers have developed a chip that helps them listen in on the signals that cancer cells send and to watch how the cells respond to their neighbors’ signals (Nano Lett., DOI: 10.1021/nl302748q).
Glioblastomas are a particularly deadly form of brain cancer owing to the tumors’ structure, says James Heath of California Institute of Technology. “They are really diffuse throughout the brain,” he says, so surgeons can’t easily remove them. It’s unclear how the cancer cells organize themselves into this diffuse pattern, but scientists suspect that they do so in part by secreting proteins that tell their cancerous neighbors where to move and whether or not to divide. Heath hypothesized that the distance between cancer cells may play a role in such cell signaling and thus may influence the structure of the tumors.
To study how distance between cancer cells affects their behavior, Heath and his colleagues designed a microchip with 8,700 chambers, each with a volume of 0.15 nL. They loaded the chip with glioblastoma cells stained with a fluorescent dye. The cells landed randomly in the chambers. Some chambers ended up with one cell, while others had two, three, or none. Using fluorescent microscopy, the researchers pinpointed the position of each cell and measured the distances between it and any other cells within its chamber.
The researchers then pressed a cover slip onto the chip. They had coated the slip with a grid of antibodies, such that over each chamber was an array of six different antibodies. Each antibody could bind a protein associated with cancer cell growth.
The team ran two experiments with these chips, one in which they held the cells on the chip with the cover slip for 30 minutes and another with a holding time of six hours. After the incubation period in both experiments, they lysed the cells and removed the cover slips to measure the concentrations of the six proteins bound by the antibodies. To do so, the researchers applied to the slip a mixture containing another set of six antibodies that could bind the proteins. Because the researchers had labeled these antibodies with fluorescent dyes, they could determine each protein’s concentration by measuring fluorescence intensity.
In the 30-minute experiment, the distance between cells didn’t affect the levels of proteins generated by each cell. But in the six-hour experiment, the researchers found that cells less than 30 µm apart responded to that proximity by producing low levels of proteins associated with tumor growth. The result, the researchers say, suggests that the cells at close distances inhibit one another. “When the cells are farther apart, they promote each other to grow,” Heath says.
Paul Mischel of the University of California, Los Angeles, says the distance results are very important and could help scientists figure out how glioblastoma tumors form. As for the microchip, he calls it a technological “step forward,” and envisions other uses in biological research, such as studying stem cell differentiation.
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