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N-(3-oxododecanoyl)-L-homoserine lactone interactions in the breast tumor microenvironment: implications for breast cancer viability and proliferation in vitro

View ORCID ProfileBrittany N. Balhouse, Logan Patterson, View ORCID ProfileEva M. Schmelz, View ORCID ProfileDaniel J. Slade, View ORCID ProfileScott S. Verbridge
doi: https://doi.org/10.1101/132092
Brittany N. Balhouse
1School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA, United States of America
2Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, United States of America
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Logan Patterson
3Department of Biochemistry, Virginia Tech, Blacksburg, VA, United States of America
4Department of Pathology, University of Virginia, Charlottesville, VA, United States of America
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Eva M. Schmelz
5Department of Human Nutrition, Foods and Exercise, Virginia Tech, Blacksburg, VA, United States of America
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Daniel J. Slade
3Department of Biochemistry, Virginia Tech, Blacksburg, VA, United States of America
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Scott S. Verbridge
1School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA, United States of America
2Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, United States of America
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  • For correspondence: sverb@vt.edu
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Abstract

It is well documented that the tumor microenvironment profoundly impacts the etiology and progression of cancer, and the contribution of the resident microbiome within breast tissue remains poorly understood. Tumor microenvironmental conditions such as hypoxia and dense tumor stroma predispose progressive phenotypes and therapy resistance, yet the role of bacteria in this interplay remains uncharacterized. We hypothesized that the effect of individual bacterial secreted molecules on breast cancer viability and proliferation would be modulated by these tumor-relevant stressors differentially for cells at varying stages of progression. To test this, we incubated human breast adenocarcinoma cells (MDA-MB-231, MCF-DCIS.com) and non-malignant breast epithelial cells (MCF-10A) with N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), a quorum-sensing molecule from Pseudomonas aeruginosa that regulates bacterial stress responses. Pseudomonas was recently characterized as a significant fraction of the breast tissue microbiome and OdDHL is documented to have significant effects on mammalian cells. We found differences in the MDA-MB-231 and MCF-DCIS.com viability after OdDHL treatment that were cell type and culture condition (i.e. microenvironment) dependent. This result was in contrast to the MCF-10A cells, which demonstrated no change in viability over the OdDHL concentration range examined, in any culture condition. We further determined that the observed trends in breast cancer viability were due to modulation of proliferation for both cell types, as well as the induction of necrosis for MDA-MB-231 cells in all conditions. Our results provide evidence that bacterial quorum-sensing molecules interact with the host environment to modulate breast cancer viability and proliferation, and that the effect of OdDHL is dependent on both cell type as well as microenvironment. Understanding the interactions between bacterial signaling molecules and the host tissue environment will allow for future studies that determine the contribution of bacteria to the onset, progression, and therapy response of breast cancer.

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Posted April 28, 2017.
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N-(3-oxododecanoyl)-L-homoserine lactone interactions in the breast tumor microenvironment: implications for breast cancer viability and proliferation in vitro
Brittany N. Balhouse, Logan Patterson, Eva M. Schmelz, Daniel J. Slade, Scott S. Verbridge
bioRxiv 132092; doi: https://doi.org/10.1101/132092
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N-(3-oxododecanoyl)-L-homoserine lactone interactions in the breast tumor microenvironment: implications for breast cancer viability and proliferation in vitro
Brittany N. Balhouse, Logan Patterson, Eva M. Schmelz, Daniel J. Slade, Scott S. Verbridge
bioRxiv 132092; doi: https://doi.org/10.1101/132092

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