Novel Insights Gained on the Process of Cancer Metastasis
Researchers at Brown University used a microengineered device that acts as an obstacle course for cells to shed new light on a cellular metamorphosis thought to play a role in tumor cell invasion throughout the body. The epithelial-mesenchymal transition (EMT) is a process in which epithelial cells, which tend to stick together within a tissue, change into mesenchymal cells, which can disperse and migrate individually.
EMT is a beneficial process in developing embryos, allowing cells to travel throughout the embryo and establish specialized tissues. But recently it has been suggested that EMT might also play a role in cancer metastasis, allowing cancer cells to escape from tumor masses and colonize distant organs.
For their study (“Collective and individual migration following the epithelial–mesenchymal transition”), published in Nature Materials, the scientists imaged cancer cells that had undergone EMT as they migrated across a device that mimics the tissue surrounding a tumor.
"People are really interested in how EMT works and how it might be associated with tumor spread, but nobody has been able to see how it happens," said lead author Ian Y. Wong, Ph.D., assistant professor in the Brown School of Engineering and the Center for Biomedical Engineering, who performed the research as a postdoctoral fellow at Massachusetts General Hospital. "We've been able to image these cells in a biomimetic system and carefully measure how they move."
The experiments showed that the cells displayed two modes of motion. A majority plod along together in a collectively advancing group, while a few cells break off from the front, covering larger distances more quickly.
“We show that EMT-activated cells migrate through micropillar arrays as a collectively advancing front that scatters individual cells,” wrote the investigators. “Individual cells with few neighbors dispersed with fast, straight trajectories, whereas cells that encountered many neighbors migrated collectively with epithelial biomarkers. We modeled these emergent dynamics using a physical analogy to phase transitions during binary-mixture solidification, and validated it using drug perturbations, which revealed that individually migrating cells exhibit diminished chemosensitivity.”
"In the context of cell migration, EMT upgrades cancer cells from an economy model to a fast sports car," noted Dr. Wong. "Our technology enabled us to track the motion of thousands of 'cars' simultaneously, revealing that many sports cars get stuck in traffic jams with the economy cars, but that some sports cars break out of traffic and make their way aggressively to distant locations."