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

<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...

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Main Authors: 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
Format: Article
Language:English
Published: Springer Science and Business Media LLC 2022
Online Access:https://hdl.handle.net/1721.1/141280
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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 MIT
description <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>
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spelling mit-1721.1/1412802022-03-19T03:20:57Z 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 <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> 2022-03-18T14:10:25Z 2022-03-18T14:10:25Z 2021 2022-03-18T14:02:49Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141280 Hamza, Bashar, Miller, Alex B, Meier, Lara, Stockslager, Max, Ng, Sheng Rong et al. 2021. "Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice." Nature Communications, 12 (1). en 10.1038/S41467-021-25917-5 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature
spellingShingle 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
url https://hdl.handle.net/1721.1/141280
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