Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice

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 ()
Additional contact information
Bashar Hamza: Massachusetts Institute of Technology
Alex B. Miller: Massachusetts Institute of Technology
Lara Meier: Massachusetts Institute of Technology
Max Stockslager: Massachusetts Institute of Technology
Sheng Rong Ng: Massachusetts Institute of Technology
Emily M. King: Massachusetts Institute of Technology
Lin Lin: Massachusetts Institute of Technology
Kelsey L. DeGouveia: Massachusetts Institute of Technology
Nolawit Mulugeta: Massachusetts Institute of Technology
Nicholas L. Calistri: Massachusetts Institute of Technology
Haley Strouf: Massachusetts Institute of Technology
Christina Bray: Massachusetts Institute of Technology
Felicia Rodriguez: Massachusetts Institute of Technology
William A. Freed-Pastor: Massachusetts Institute of Technology
Christopher R. Chin: Massachusetts Institute of Technology
Grissel C. Jaramillo: Massachusetts Institute of Technology
Megan L. Burger: Massachusetts Institute of Technology
Robert A. Weinberg: Massachusetts Institute of Technology
Alex K. Shalek: Massachusetts Institute of Technology
Tyler Jacks: Massachusetts Institute of Technology
Scott R. Manalis: Massachusetts Institute of Technology

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Existing preclinical methods for acquiring dissemination kinetics of rare circulating tumor cells (CTCs) en route to forming metastases have not been capable of providing a direct measure of CTC intravasation rate and subsequent half-life in the circulation. Here, we demonstrate an approach for measuring endogenous CTC kinetics by continuously exchanging CTC-containing blood over several hours between un-anesthetized, tumor-bearing mice and healthy, tumor-free counterparts. By tracking CTC transfer rates, we extrapolated half-life times in the circulation of between 40 and 260 s and intravasation rates between 60 and 107,000 CTCs/hour in mouse models of small-cell lung cancer (SCLC), pancreatic ductal adenocarcinoma (PDAC), and non-small cell lung cancer (NSCLC). Additionally, direct transfer of only 1−2% of daily-shed CTCs using our blood-exchange technique from late-stage, SCLC-bearing mice generated macrometastases in healthy recipient mice. We envision that our technique will help further elucidate the role of CTCs and the rate-limiting steps in metastasis.

Date: 2021
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DOI: 10.1038/s41467-021-25917-5

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