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From microfluidics to metastasis
Ludwig MIT investigators report a new technology to study circulating tumor cells and tumor evolution in mouse models of cancer.
January 28, 2019, New York— Researchers at the Ludwig Center at MIT and the Koch Institute have developed a pioneering approach to isolating circulating tumor cells (CTCs) from mice in real time. The system, described in the current issue of the Proceedings of the National Academy of Sciences, diverts blood to a microfluidic cell-sorting chip that extracts individual CTCs—an intermediate form of cancer cell between a primary and metastatic tumor cell—before returning the blood to an awake mouse. This allows researchers to collect CTCs over days, and even weeks, to analyze the CTCs as the cancer progresses, a capability that should contribute significantly to the study of tumor metastasis. The study was led by Ludwig MIT and Koch Institute investigators Tyler Jacks and Scott Manalis, and their Koch colleague Alex K. Shalek.
CTCs carry a trove of genomic information about a cancer and its progression, and many researchers and companies are developing technologies to isolate and analyze the rare cells to inform and improve the diagnosis and treatment of cancer patients. But such “liquid biopsies” hold great promise for the lab as well. Mouse models mimic many aspects of human tumor development and can be used to trace the evolution of tumor cells from initial mutation to metastasis—a process in which CTCs often play a central role. But since it has not been possible to monitor CTCs over time in mice, scientists’ ability to study important features of metastasis has been limited.
The challenge lies in capturing enough cells to conduct such longitudinal studies, since a mouse only has about 1.5 milliliters of blood in total. If researchers want to study CTCs over time, they may safely withdraw no more than a few microliters of blood from a mouse each day—nowhere near enough to ensure that many (or any) CTCs are collected.
The CTC sorter developed in the study uses laser excitation to identify tumor cells expressing a fluorescent marker that is incorporated in the mouse model. The system draws blood from the mouse and passes it through a microfluidic chip to detect and extract the fluorescing CTCs before returning the blood to the mouse. A minute amount of blood—approximately 100 nanoliters—is diverted with every detected CTC into a collection tube, which then is purified further to extract individual CTCs from the thousands of other blood cells.
The researchers believe their approach, which they intend to use in additional cancer types including non-small cell lung, pancreatic, and breast cancer, could open new avenues of inquiry, such as studying long-term drug responses and the entire metastatic cascade. They also plan to use their approach to profile rare immune cells and monitor cells in dynamic processes, such as wound healing and tumor formation.
The MIT news release from which this summary is derived can be found here.