Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice
Author(s)
Hamza, Bashar; Miller, Alex B.; Meier, Lara; Stockslager, Max; Ng, Sheng Rong; King, Emily M.; Lin, Lin; DeGouveia, Kelsey L.; Mulugeta, Nolawit; Calistri, Nicholas L.; Strouf, Haley; Bray, Christina; Rodriguez, Felicia; Freed-Pastor, William A.; Chin, Christopher R.; Jaramillo, Grissel C.; Burger, Megan L.; Weinberg, Robert A.; Shalek, Alex K.; Jacks, Tyler; Manalis, Scott R.; ... Show more Show less
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<jats:title>Abstract</jats:title><jats:p>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.</jats:p>
Date issued
2021-09Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science; Koch Institute for Integrative Cancer Research at MIT; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Massachusetts Institute of Technology. Department of Mechanical Engineering; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Biological Engineering; Whitehead Institute for Biomedical Research; Massachusetts Institute of Technology. Department of Chemistry; Ragon Institute of MGH, MIT and Harvard; Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology)Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Hamza, Bashar, Miller, Alex B, Meier, Lara, Stockslager, Max, Ng, Sheng Rong et al. 2021. "Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice." Nature Communications, 12 (1).
Version: Final published version
ISSN
2041-1723