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

By Bashar Hamza, Alex B. Miller, Lara Meier, Max Stockslager, Emily M. King, Sheng Rong Ng, Kelsey L. DeGouveia, Nolawit Mulugeta, Nicholas L Calistri, Haley Strouf, Lin Lin, Christopher R. Chin, Robert Weinberg, Alex K Shalek, Tyler Jacks, Scott Manalis

Posted 01 Nov 2020
bioRxiv DOI: 10.1101/2020.11.01.350918

Existing pre-clinical 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 using an autochthonous small cell lung cancer model, we extrapolated half-life times in the circulation of 50-100 seconds and intravasation rates between 4,000 and 27,000 CTCs/hour − an average daily shedding rate equivalent to ~0.07% of the total number of primary tumor cells in the lung. Additionally, transfer of 1-2% of daily-shed CTCs from late-stage tumor-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 ### Competing Interest Statement The authors have declared no competing interest.

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