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Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice
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 meas...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479082/ https://www.ncbi.nlm.nih.gov/pubmed/34584084 http://dx.doi.org/10.1038/s41467-021-25917-5 |
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author | Hamza, Bashar Miller, Alex B. Meier, Lara Stockslager, Max Ng, Sheng Rong King, Emily M. Lin, Lin DeGouveia, Kelsey L. Mulugeta, Nolawit Calistri, Nicholas L. Strouf, Haley Bray, Christina Rodriguez, Felicia Freed-Pastor, William A. Chin, Christopher R. Jaramillo, Grissel C. Burger, Megan L. Weinberg, Robert A. Shalek, Alex K. Jacks, Tyler Manalis, Scott R. |
author_facet | Hamza, Bashar Miller, Alex B. Meier, Lara Stockslager, Max Ng, Sheng Rong King, Emily M. Lin, Lin DeGouveia, Kelsey L. Mulugeta, Nolawit Calistri, Nicholas L. Strouf, Haley Bray, Christina Rodriguez, Felicia Freed-Pastor, William A. Chin, Christopher R. Jaramillo, Grissel C. Burger, Megan L. Weinberg, Robert A. Shalek, Alex K. Jacks, Tyler Manalis, Scott R. |
author_sort | Hamza, Bashar |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8479082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84790822021-10-22 Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice Hamza, Bashar Miller, Alex B. Meier, Lara Stockslager, Max Ng, Sheng Rong King, Emily M. Lin, Lin DeGouveia, Kelsey L. Mulugeta, Nolawit Calistri, Nicholas L. Strouf, Haley Bray, Christina Rodriguez, Felicia Freed-Pastor, William A. Chin, Christopher R. Jaramillo, Grissel C. Burger, Megan L. Weinberg, Robert A. Shalek, Alex K. Jacks, Tyler Manalis, Scott R. Nat Commun Article 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. Nature Publishing Group UK 2021-09-28 /pmc/articles/PMC8479082/ /pubmed/34584084 http://dx.doi.org/10.1038/s41467-021-25917-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Hamza, Bashar Miller, Alex B. Meier, Lara Stockslager, Max Ng, Sheng Rong King, Emily M. Lin, Lin DeGouveia, Kelsey L. Mulugeta, Nolawit Calistri, Nicholas L. Strouf, Haley Bray, Christina Rodriguez, Felicia Freed-Pastor, William A. Chin, Christopher R. Jaramillo, Grissel C. Burger, Megan L. Weinberg, Robert A. Shalek, Alex K. Jacks, Tyler Manalis, Scott R. Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice |
title | Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice |
title_full | Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice |
title_fullStr | Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice |
title_full_unstemmed | Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice |
title_short | Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice |
title_sort | measuring kinetics and metastatic propensity of ctcs by blood exchange between mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479082/ https://www.ncbi.nlm.nih.gov/pubmed/34584084 http://dx.doi.org/10.1038/s41467-021-25917-5 |
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