A microchip for metastasis

MIT researchers design a microfluidic platform to see how cancer cells invade specific organs

Researchers from Massachusetts Institute of Technology (MIT) in the US, as well as Italy and South Korea, have developed a three-dimensional microfluidic platform that mimics the spread of breast cancer cells into a bonelike environment.

The microchip — slightly larger than a dime — contains several channels in which the researchers grew endothelial and bone cells to mimic a blood vessel and bone side-by-side. They then injected a highly metastatic line of breast cancer cells into the fabricated blood vessel.

Twenty-four hours later, the team observed that twice as many cancer cells had made their way through the vessel wall and into the bonelike environment than had migrated into a simple collagen-gel matrix. Moreover, the cells that made it through the vessel lining and into the bonelike setting formed microclusters of up to 60 cancer cells by the experiment’s fifth day.

'You can see how rapidly they are growing,' said Jessie Jeon, a graduate student in mechanical engineering. 'We only waited until day five, but if we had gone longer, [the size of the clusters] would have been overwhelming.'

The team also identified two molecules that appear to encourage cancer cells to metastasize: CXCL5, a protein ligand secreted by bone cells, and CXCR2, a receptor protein on cancer cells that binds to the ligand. The preliminary results suggest that these molecules may be potential targets to reduce the spread of cancer.

One might envision using cells from the cancer patient to produce models of different organs

Jeon said the experiments demonstrate that the microchip may be used in the future to test drugs that might stem metastasis, and also as a platform for studying cancer’s spread to other organs.

She and her colleagues, including Roger Kamm, the Cecil and Ida Green Distinguished Professor of Mechanical and Biological Engineering at MIT, have outlined the results of their experiments in the journal Biomaterials.

'Currently, we don't understand why certain cancers preferentially metastasize to specific organs,' Kamm said. 'An example is that breast cancer will form metastatic tumours in bone, but not, for example, in muscle. Why is this, and what factors determine it? We can use our model system both to understand this selectivity, and also to screen for drugs that might prevent it.'

The process by which cancer cells form secondary tumours requires the cells first to survive a journey through the circulatory system. These migrating cells attach to a blood vessel’s inner lining, and ultimately squeeze through to the surrounding tissue — a process called extravasation, which Kamm’s research group modelled in Autumn 2013 using a novel microfluidic platform.

The team now plans to explore cancer metastasis in other organs, such as muscle — an organ in which cancer cells do not easily spread.

'There are some organs known to be more or less metastatic, and if we can add two different organ types, we can see what kind of differences there are,' Jeon said.

Kamm added that in the future, such a platform may be used in personalised medicine to determine the best cancer therapy for a given patient.

'One might envision using cells from the cancer patient to produce models of different organs, then using these models to determine the optimal therapy from a variety of available drugs,' he said.

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