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

Nat Commun. 2021 Sep 28;12(1):5680. doi: 10.1038/s41467-021-25917-5.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Transfusion / methods
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Pancreatic Ductal / blood
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Line, Tumor
  • Humans
  • Kinetics
  • Lung Neoplasms / blood
  • Lung Neoplasms / pathology*
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / pathology*
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / pathology*
  • Propensity Score
  • RNA-Seq / methods
  • Single-Cell Analysis / methods
  • Small Cell Lung Carcinoma / blood
  • Small Cell Lung Carcinoma / pathology*

Supplementary concepts

  • Pancreatic Carcinoma