PT  - JOURNAL ARTICLE
AU  - Lauren E. Hillers-Ziemer
AU  - Abbey E. Williams
AU  - Amanda Janquart
AU  - Caitlin Grogan
AU  - Victoria Thompson
AU  - Adriana Sanchez
AU  - Lisa M. Arendt
TI  - Obesity-Activated Lung Stomal Cells Promote Myeloid-Lineage Cell Accumulation and Breast Cancer Metastasis
AID  - 10.1101/2020.11.23.394387
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.23.394387
4099  - http://biorxiv.org/content/early/2020/11/23/2020.11.23.394387.short
4100  - http://biorxiv.org/content/early/2020/11/23/2020.11.23.394387.full
AB  - 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 StatementThe authors have declared no competing interest.