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

• Main Authors: Hamza, Bashar (Author), Miller, Alex B (Author), Meier, Lara (Author), Stockslager, Max (Author), Ng, Sheng Rong (Author), King, Emily M (Author), Lin, Lin (Author), DeGouveia, Kelsey L (Author), Mulugeta, Nolawit (Author), Calistri, Nicholas L (Author), Strouf, Haley (Author), Bray, Christina (Author), Rodriguez, Felicia (Author), Freed-Pastor, William A (Author), Chin, Christopher R (Author), Jaramillo, Grissel C (Author), Burger, Megan L (Author), Weinberg, Robert A (Author), Shalek, Alex K (Author), Jacks, Tyler (Author), Manalis, Scott R (Author)
• Format: Article
• Language: English
• Published: Springer Science and Business Media LLC, 2022-03-18T14:10:25Z.
• Subjects: Article
• Online Access: Get fulltext

<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>