Nearly 70 percent of patients with advanced breast cancer experience skeletal metastasis, in which cancer cells migrate from a primary tumor into bone — a painful development that can cause fractures and spinal compression. While scientists are attempting to better understand metastasis in general, not much is known about how and why certain cancers spread to specific organs, such as bone, liver, and lungs.
Now researchers from MIT, 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 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.
“You can see how rapidly they are growing,” says 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 says 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....