MIT's technology to reveal how cancer spreads

For the first time, MIT engineers have developed a technique that allows them to count tumor cells and measure the rate and half-life of circulating tumor cells (CTCs)

MIT engineers devised a method to count elusive circulating tumor cells in mice, allowing them to study the dynamics of metastasis

When tumors grow in organs, they also release cells that enter the blood

MIT engineers have now developed a technique that is the first time they can measure the rate of generation of circulating tumor cells (CTCs) in mice

"By exchanging blood between mice and simultaneously counting CTCs in real time, we obtain a direct measurement of the speed at which CTCs enter the circulation and how long it takes for them to be cleared," Professor of Engineering in the Department of Bioengineering and Mechanical Engineering, Koch General Said Scott Manalis, a member of the Cancer Institute and senior author of the study

Using their new system, researchers were able to study CTCs from pancreatic tumors and two types of lung tumors

Koch Institute graduate student Alex Miller and visiting scientist Dr.

Capture rare cells

Circulating tumor cells are rare in patients: 1 ml of blood may contain 1 to 10 circulating tumor cells

"Circulating tumor cells are attractive because you can get them from the blood.

In mice, CTCs are more difficult to find, because mice only have a little more than 1 ml of blood

To answer these questions, Manalis and his students designed a system that allows them to draw blood from mice with tumors and inject it into healthy mice

Using this device, researchers can analyze all the blood of each mouse in less than an hour

The researchers worked with members of the Jacks laboratory at the Koch Institute to use the system to study mice with three different types of tumors: pancreatic cancer, small cell lung cancer, and non-small cell lung cancer

They found that the half-lives of CTCs between the three tumors were quite similar, ranging from 40 seconds to 250 seconds

Previous studies have relied on injecting tumor cells from cell lines cultured in the laboratory and found that these cells have a half-life of only a few seconds in the blood, but the new results of the Hamza laboratory show that endogenous CTCs actually exist for longer than this.

Generate transfer

The researchers also showed that healthy mice that received CTCs later metastasized, even if only a few thousand CTCs were exchanged

Hamza said: “We realized that the CTCs that we injected into healthy recipient mice started to grow and produced metastases that we could detect within a few months
.
This is an exciting observation because it validates Our blood exchange technology can also be used to gently inject a viable sample of CTCs in its local blood environment without using harsh extracorporeal techniques to enrich it
.
"

Using this method, researchers now hope to study how different drug treatments affect CTCs levels
.
Miller said: "With this system, we can observe the real-time concentration of CTCs, so that we can perform drug treatments and observe how it affects the half-life and production rate
.
"

Researchers also plan to use the system to study other types of cancer, including blood cancers such as leukemia and lymphoma
.
The technology can also be used to study the circulation dynamics of other types of cells, including immune cells such as neutrophils and natural killer cells
.

"Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice" by Bashar Hamza, Alex B.
Miller, Lara Meier, Max Stockslager, Sheng Rong Ng, Emily M.
King, Lin Lin, Kelsey L.
DeGouveia, Nolawit Mulugeta, Nicholas L.
Calistri, Haley Strouf, Christina Bray, Felicia Rodriguez, William A.
Freed-Pastor, Christopher R.
Chin, Grissel C.
Jaramillo, Megan L.
Burger, Robert A.
Weinberg, Alex K.
Shalek, Tyler Jacks and Scott R .
Manalis, 28 September 2021, Nature Communications .

DOI: 10.
1038/s41467-021-25917-5