MIT researchers develop chip to study metastasis
With the aim of gaining deeper understanding as to how cancers spread to specific organs such as bone, liver and lungs, researchers from MIT, Italy and South Korea have developed a 3D 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 cells 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.
A 3D reconstruction of a confocal image for a bone-mimicking microenvironment (green). Endothelial cells (red), mimic blood vessels, with breast cancer cells (blue) passing through the endothelial wall, into the bone-like matrix. Photo: Jessie Jeon.
"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.
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 stated. "An example is that breast cancer will form metastatic tumors in bone, but not, for example, 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 tumors requires the cells to first 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 last fall using a novel microfluidic platform.
|Related Articles||Editor's Choice|