MGH-developed microfluidic can help study the major steps involved in the development of tumor metastases -
A microfluidic device developed at the Massachusetts General Hospital (MGH) may help study main steps of the process by which cancer cells detach from the primary tumor to invade other tissues and metastasize. In their report published in Nature Materials , the researchers describe a stand for the epithelial-mesenchymal transition, a fundamental change in cellular characteristics that were associated with the ability of tumor cells to migrate and invade other sites in the body. Therapies that target this process may be able to slow or stop tumor metastasis.
"This system gives us a platform to be used in testing and comparison of compounds to block or delay the epithelial-mesenchymal transition, which could slow the progression of cancer," said Daniel Irimia , MD, PhD, associate director of the BioMEMS resource Center in the MGH department of surgery.
Normally, a step in embryonic development, EMT is important during the healing of normal wound and also seems to take place when the epithelial cells that line the body cavities and surfaces become malignant. instead of adhering to each other tightly in layers of cells that have undergone EMT acquire the ability to separate, to move to other parts of the body and settle in new sites. cells that have made the transition to a mesenchymal state seem to be more resistant to cancer treatment or other measures to induce cell death.
The device developed at MGH allows investigator to follow the movement of the cells through a comb-like array of micropillars that temporarily separates the cells adhere to each other. To establish the basic characteristics of non-cancerous cells, the researchers first studied the passage of normal epithelial cells through the network. They observed that the cells moved at the same speed as the neighboring cells, reconnect when they come into contact with each other multicellular sheets that break repeatedly outside and close. Tumor cells, however, passed rapidly and directly through the device and do not interact with neighboring cells.
When cells in which the EMT process was initiated by genetic manipulation were seen passing through the device, at first they migrated collectively. But soon after meeting the first micropillars, many cells are separated from the front group and individually migrated to the rest of their trajectory. Some cells appeared to undergo the opposite transition, returning from the individual return migration collective migration. Further analysis revealed that the slower moving cells that continued migration of epithelial markers whole cast, while the fastest moving cells migrate independently expressed mesenchymal markers. Individual cells migrating also seemed to be more resistant to treatment with chemotherapy drugs.
A particular advantage of the EMT chip is the ability to observe how the behavior of a cell population changes over time. "Instead of providing a snapshot of cells or tissue at a given time, than traditional histological studies do, the new chip can capture the changing dynamics of individual or collective cell migration," says Irimia, assistant professor of surgery at Harvard Medical School. "in the controlled environment of the EMT chip, these processes like these phase transitions that change from solid to liquid that occurs with the merger. Analogies with well-studied physical processes are very useful to summarize the EMT complex process in some settings. These parameters are useful for comparison between different types of cells and to study the contribution of various biological processes EMT. They are also useful when comparing different chemicals to discover new compounds to block or delay EMT "
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