1. Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice.
- Author
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Hamza B, Miller AB, Meier L, Stockslager M, Ng SR, King EM, Lin L, DeGouveia KL, Mulugeta N, Calistri NL, Strouf H, Bray C, Rodriguez F, Freed-Pastor WA, Chin CR, Jaramillo GC, Burger ML, Weinberg RA, Shalek AK, Jacks T, and Manalis SR
- Subjects
- Animals, Blood Transfusion methods, Carcinoma, Non-Small-Cell Lung blood, Carcinoma, Pancreatic Ductal blood, Cell Line, Tumor, Humans, Kinetics, Lung Neoplasms blood, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Neoplasm Metastasis, Pancreatic Neoplasms blood, Propensity Score, RNA-Seq methods, Single-Cell Analysis methods, Small Cell Lung Carcinoma blood, Mice, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Pancreatic Ductal pathology, Lung Neoplasms pathology, Neoplastic Cells, Circulating pathology, Pancreatic Neoplasms pathology, Small Cell Lung Carcinoma pathology
- Abstract
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., (© 2021. The Author(s).)
- Published
- 2021
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