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MIT engineers have now developed a technique that is the first time they can measure the rate of production of circulating tumor cells (ctc) in mice
"By exchanging blood between mice while counting ctc in real time, we obtain a direct measurement of how quickly ctc enters the circulation and how long it takes for them to be cleared," David H.
Using their new system, researchers were able to study ctc from pancreatic tumors and two types of lung tumors
Graduate student Alex Miller and Koch Institute visiting scientist, 20-year-old Ph.
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, ctc is 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 Jack Lab of 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 ctc between the three tumors were quite similar, ranging from 40 seconds to 250 seconds
Previous research relied on injecting tumor cells from cell lines cultured in the laboratory and found that these cells only have a half-life of a few seconds in the blood, but new results from the Manalis laboratory show how long endogenous ctc actually exists.
Generate transfer
The researchers also showed that healthy mice that received ctc later metastasized, even if only a few thousand ctc were exchanged
Hamza said: "We realized that the ctc we injected into healthy recipient mice began to grow and produce metastases that we could detect within a few months
Using this method, researchers now hope to study how different drug treatments affect CTC levels
Researchers also plan to use the system to study other types of cancer, including blood cancers such as leukemia and lymphoma
This research was funded by the Virginia and DK Ludwig Cancer Research Fund, the Alliance for Cancer Systems Biology, the National Cancer Institute, the Pew-Stewart Cancer Research Scholars Program, the Sloan Chemistry Fellowship, and the National Institutes of Health
.
Journal Reference :
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, Scott R.
Manalis.
Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice .
Nature Communications , 2021; 12 (1) DOI: 10.
1038/s41467-021-25917-5