Cancer cells have a built-in drive to explore and will determinedly travel for hours on end without any external guidance, a new device that shows their movement has revealed. This kind of knowledge could help develop new strategies against the disease.
Secondary tumours, or metastases, form when cancer cells migrate through the body and found new tumours. They are responsible for 90 per cent of cancer-associated deaths.
Yet most treatments try to destroy only existing tumours or limit their growth, says Daniel Irimia at Massachusetts General Hospital in Boston and Harvard Medical School. With his colleague Mehmet Toner he built a device to reveal the travelling tendencies of cancer cells, believing that this could open new fronts in the war on the disease.
Irimia and Toner made a large number of plastic "chips" shot through with a series of microscopic channels 6 to 100 micrometres wide and lined with proteins like those found in connective tissue, such as collagen. The progress of cells down the channels can be tracked under a microscope.
The researchers seeded the devices with human cancer cells, including cells of lung, prostate and breast cancer. "We thought that by confining cancer cells in small channels in the presence of [chemical] gradients we could better replicate the mechanical and chemical interactions that these cells have inside tissues," Irimia says.
The first results were unexpected. Cells of all kinds, whether healthy or diseased, typically navigate by using chemical gradients – differences in chemical concentrations – as navigation beacons. But even in control devices without such gradients most cancer cells tested began to head in one direction along the channels without stopping, some for more than 12 hours.
Without an external signal, cells normally move back and forth randomly, says Irimia. "A directional clue [such as] a chemical gradient would be needed to bias that random behaviour towards one direction." But the cancer cells, he says, seem to be self-guided.
Further experiments with the device revealed more surprises. The researchers tested the effect of paclitaxel, sold as Taxol, a chemotherapy drug used to prevent a tumour''s cell population growing, expecting it to have some effect on cell movement.
But even at concentrations more than high enough to prevent tumour growth some cancer cells continued to migrate quickly through the channels.
That''s an alarming result, says Irimia. "Our current knowledge suggests that one cell is enough to start a metastasis if all conditions are right; what individual cells do is more important in cancer than what the average cell population does."
Irimia says that by allowing researchers to measure the motility of cancer cells the new device could help to develop and test new anti-motility drugs.
Journal reference: Integrative Biology, DOI: 10.1039/b908595e