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Obesity-Activated Lung Stomal Cells Promote Myeloid-Lineage Cell Accumulation and Breast Cancer Metastasis

Lauren E. Hillers-Ziemer, Abbey E. Williams, Amanda Janquart, Caitlin Grogan, Victoria Thompson, Adriana Sanchez, View ORCID ProfileLisa M. Arendt
doi: https://doi.org/10.1101/2020.11.23.394387
Lauren E. Hillers-Ziemer
1Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison WI 53706, USA
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Abbey E. Williams
2Program in Comparative Biomedical Sciences, University of Wisconsin-Madison, Madison WI 53706, USA
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Amanda Janquart
3Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison WI 53706, USA
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Caitlin Grogan
3Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison WI 53706, USA
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Victoria Thompson
3Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison WI 53706, USA
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Adriana Sanchez
3Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison WI 53706, USA
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Lisa M. Arendt
1Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison WI 53706, USA
2Program in Comparative Biomedical Sciences, University of Wisconsin-Madison, Madison WI 53706, USA
3Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison WI 53706, USA
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  • ORCID record for Lisa M. Arendt
  • For correspondence: lmarendt@wisc.edu
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SUMMARY

Obesity is correlated with increased incidence of breast cancer metastasis, however the mechanisms underlying how obesity promotes metastasis are unclear. In a diet-induced obesity mouse model, obesity enhanced lung metastases in both the presence and absence of primary mammary tumors and increased recruitment of myeloid lineage cells into the lungs. In the absence of tumors, obese mice demonstrated increased numbers of myeloid lineage cells and elevated collagen fibers within the lung stroma, reminiscent of pre-metastatic niches formed by primary tumors. Lung stromal cells isolated from obese non-tumor-bearing mice showed increased proliferation, contractility, and expression of extracellular matrix, inflammatory markers, and TGFβ1. Conditioned media from lung stromal cells from obese mice promoted myeloid lineage cell migration in vitro in response to CSF2 expression and enhanced invasion of tumor cells. Together, these results suggest that prior to tumor formation, obesity alters the lung microenvironment, creating niches conducive for metastatic growth.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 23, 2020.
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Obesity-Activated Lung Stomal Cells Promote Myeloid-Lineage Cell Accumulation and Breast Cancer Metastasis
Lauren E. Hillers-Ziemer, Abbey E. Williams, Amanda Janquart, Caitlin Grogan, Victoria Thompson, Adriana Sanchez, Lisa M. Arendt
bioRxiv 2020.11.23.394387; doi: https://doi.org/10.1101/2020.11.23.394387
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Obesity-Activated Lung Stomal Cells Promote Myeloid-Lineage Cell Accumulation and Breast Cancer Metastasis
Lauren E. Hillers-Ziemer, Abbey E. Williams, Amanda Janquart, Caitlin Grogan, Victoria Thompson, Adriana Sanchez, Lisa M. Arendt
bioRxiv 2020.11.23.394387; doi: https://doi.org/10.1101/2020.11.23.394387

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