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Comparing the fate of brain metastatic breast cancer cells in different immune compromised mice with cellular magnetic resonance imaging

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Abstract

Metastasis is the leading cause of mortality in breast cancer patients, with brain metastases becoming increasingly prevalent. Studying this disease is challenging due to the limited experimental models and methods available. Here, we used iron-based cellular MRI to track the fate of a mammary carcinoma cell line (MDA-MB-231-BR) in vivo to characterize the growth of brain metastases in the nude and severely immune-compromised NOD/SCID/ILIIrg−/− (NSG) mouse. Nude and NSG mice received injections of iron-labeled MDA-MB-231-BR cells. Images were acquired with a 3T MR system and assessed for signal voids and metastases. The percentage of signal voids and the number and volume of metastases were quantified. Ex vivo imaging of the liver, histology, and immunofluorescence labeling was performed. Brain metastases grew more rapidly in NSG mice. At day 21 post cell injection, the average number of brain tumors in NSG mice was approximately four times greater than in nude mice. The persistence of iron-labeled cells, visualized as signal voids by MRI, was also examined. The percentage of voids decreased significantly over time for both nude and NSG mice. Body images revealed that the NSG mice also had metastases in the liver, lungs, and lymph nodes while tumors were only detected in the brains of nude mice. This work demonstrates the advantages of using the highly immune-compromised NSG mouse to study breast cancer metastasis, treatments aimed at inhibiting metastasis and outgrowth of breast cancer metastases in multiple organs, and the role that imaging can play toward credentialing these models that cannot be done with other in vitro or histopathologic methods alone.

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

bSSFP:

Balanced steady-state free precession

BW:

Bandwidth

DMEM:

Dulbecco’s modified Eagle’s medium

FA:

Flip angle

FACS:

Fluorescence activated cell sorting

FIESTA:

Fast imaging employing steady state acquisition

GFP:

Green fluorescent protein

H&E:

Hematoxylin and eosin

MPIO:

Micron-sized iron oxide particles

MRI:

Magnetic resonance imaging

NSG:

NOD/SCID/ILIIrg−/−

PBS:

Perl’s Prussian Blue

PDX:

Patient-derived xenograft

RF:

Radiofrequency

TE:

Echo time

TR:

Repetition time

US:

Ultrasound

231BR:

MDA-MB-231BR

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Acknowledgements

The authors would like to thank Ashley V. Makela for assisting with mouse injections for this study and the Canadian Institute for Health Research and the Breast Cancer Society of Canada for their funding.

Funding

This study was supported by the Canadian Institute for Health Research (P.J. Foster) and the Breast Cancer Society of Canada (N.N. Knier).

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Authors and Affiliations

  1. Imaging Research Laboratories, Robarts Research Institute, 1151 Richmond St. N., London, ON, N6A 5B7, Canada

    Natasha N. Knier, Amanda M. Hamilton & Paula J. Foster

  2. Department of Medical Biophysics, Western University, 1151 Richmond St, London, ON, N6A 3K7, Canada

    Natasha N. Knier & Paula J. Foster

Authors
  1. Natasha N. Knier
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  2. Amanda M. Hamilton
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  3. Paula J. Foster
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Contributions

PJF designed the experiments. NNK, PJF, and AMH conducted the experiments. NNK analyzed the data. NNK and PJF wrote the main manuscript text. All authors reviewed the manuscript.

Corresponding author

Correspondence to Natasha N. Knier.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

Animals were cared for in accordance with the standards of the Canadian Council on Animal. Care, and under an approved protocol of the Western University’s Council on Animal Care (2018-135).

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Knier, N.N., Hamilton, A.M. & Foster, P.J. Comparing the fate of brain metastatic breast cancer cells in different immune compromised mice with cellular magnetic resonance imaging. Clin Exp Metastasis 37, 465–475 (2020). https://doi.org/10.1007/s10585-020-10044-0

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  • DOI: https://doi.org/10.1007/s10585-020-10044-0

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