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Title: Tracking Tumor Colonization in Xenograft Mouse Models Using Accelerator Mass Spectrometry [Tracking Tumor Colonization in vivo Using Accelerator Mass Spectrometry]

Abstract

Here we propose an Accelerator Mass Spectrometry (AMS)-based high precision method for quantifying the number of cancer cells that initiate metastatic tumors, in xenograft mice. Quantification of 14C per cell prior to injection into animals, and quantification of 14C in whole organs allows us to extrapolate the number of cancer cells available to initiate metastatic tumors. The 14C labeling was optimized such that 1 cancer cell was detected among 1 million normal cells. We show that ~1–5% of human cancer cells injected into immunodeficient mice form subcutaneous tumors, and even fewer cells initiate metastatic tumors. Comparisons of metastatic site colonization between a highly metastatic (PC3) and a non-metastatic (LnCap) cell line showed that PC3 cells colonize target tissues in greater quantities at 2 weeks post-delivery, and by 12 weeks post-delivery no 14C was detected in LnCap xenografts, suggesting that all metastatic cells were cleared. The 14C-signal correlated with the presence and the severity of metastatic tumors. AMS measurements of 14C-labeled cells provides a highly-sensitive, quantitative assay to experimentally evaluate metastasis and colonization of target tissues in xenograft mouse models. This method can potentially be used to evaluate tumor aggressiveness and assist in making informed decisions regarding treatment.

Authors:
 [1];  [2];  [1];  [1];  [1];  [3]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  2. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Georgetown Univ., Washington, DC (United States)
  3. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Univ. of California Merced, Merced, CA (United States)
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1527297
Report Number(s):
LLNL-JRNL-730778
Journal ID: ISSN 2045-2322; 881776
Grant/Contract Number:  
AC52-07NA27344
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Hum, Nicholas R., Martin, Kelly A., Malfatti, Michael A., Haack, Kurt, Buchholz, Bruce A., and Loots, Gabriela G. Tracking Tumor Colonization in Xenograft Mouse Models Using Accelerator Mass Spectrometry [Tracking Tumor Colonization in vivo Using Accelerator Mass Spectrometry]. United States: N. p., 2018. Web. doi:10.1038/s41598-018-33368-0.
Hum, Nicholas R., Martin, Kelly A., Malfatti, Michael A., Haack, Kurt, Buchholz, Bruce A., & Loots, Gabriela G. Tracking Tumor Colonization in Xenograft Mouse Models Using Accelerator Mass Spectrometry [Tracking Tumor Colonization in vivo Using Accelerator Mass Spectrometry]. United States. doi:10.1038/s41598-018-33368-0.
Hum, Nicholas R., Martin, Kelly A., Malfatti, Michael A., Haack, Kurt, Buchholz, Bruce A., and Loots, Gabriela G. Tue . "Tracking Tumor Colonization in Xenograft Mouse Models Using Accelerator Mass Spectrometry [Tracking Tumor Colonization in vivo Using Accelerator Mass Spectrometry]". United States. doi:10.1038/s41598-018-33368-0. https://www.osti.gov/servlets/purl/1527297.
@article{osti_1527297,
title = {Tracking Tumor Colonization in Xenograft Mouse Models Using Accelerator Mass Spectrometry [Tracking Tumor Colonization in vivo Using Accelerator Mass Spectrometry]},
author = {Hum, Nicholas R. and Martin, Kelly A. and Malfatti, Michael A. and Haack, Kurt and Buchholz, Bruce A. and Loots, Gabriela G.},
abstractNote = {Here we propose an Accelerator Mass Spectrometry (AMS)-based high precision method for quantifying the number of cancer cells that initiate metastatic tumors, in xenograft mice. Quantification of 14C per cell prior to injection into animals, and quantification of 14C in whole organs allows us to extrapolate the number of cancer cells available to initiate metastatic tumors. The 14C labeling was optimized such that 1 cancer cell was detected among 1 million normal cells. We show that ~1–5% of human cancer cells injected into immunodeficient mice form subcutaneous tumors, and even fewer cells initiate metastatic tumors. Comparisons of metastatic site colonization between a highly metastatic (PC3) and a non-metastatic (LnCap) cell line showed that PC3 cells colonize target tissues in greater quantities at 2 weeks post-delivery, and by 12 weeks post-delivery no 14C was detected in LnCap xenografts, suggesting that all metastatic cells were cleared. The 14C-signal correlated with the presence and the severity of metastatic tumors. AMS measurements of 14C-labeled cells provides a highly-sensitive, quantitative assay to experimentally evaluate metastasis and colonization of target tissues in xenograft mouse models. This method can potentially be used to evaluate tumor aggressiveness and assist in making informed decisions regarding treatment.},
doi = {10.1038/s41598-018-33368-0},
journal = {Scientific Reports},
number = 1,
volume = 8,
place = {United States},
year = {2018},
month = {10}
}

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