Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice
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s41467-021-25917-5.pdf
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Published version
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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.
Date Issued
September 2021
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
Abstract
AbstractExisting 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.
MIT Department
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)
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s41467-021-25917-5