Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice
Alex B. Miller,
Emily M. King,
Sheng Rong Ng,
Kelsey L. DeGouveia,
Nicholas L Calistri,
Christopher R. Chin,
Alex K Shalek,
Posted 01 Nov 2020
bioRxiv DOI: 10.1101/2020.11.01.350918
Posted 01 Nov 2020
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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