Tumor-stroma interactions differentially alter drug sensitivity based on the origin of stromal cells
AuthorsLandry, Benjamin D.
Honeywell, Megan E.
Schwartz, Alyssa D.
Peyton, Shelly R.
Lee, Michael J.
UMass Chan AffiliationsDepartment of Molecular, Cell and Cancer Biology
Program in Molecular Medicine
Program in Systems Biology
Document TypeJournal Article
triple‐negative breast cancer
Genetics and Genomics
MetadataShow full item record
AbstractDue to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear, however, what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor microenvironment. Using a large-scale coculture assay optimized to measure drug-induced cell death, we identify tumor-stroma interactions that modulate drug sensitivity. Our data show that the chemo-insensitivity typically associated with aggressive subtypes of breast cancer is not observed if these cells are grown in 2D or 3D monoculture, but is manifested when these cells are cocultured with stromal cells, such as fibroblasts. Furthermore, we find that fibroblasts influence drug responses in two distinct and divergent manners, associated with the tissue from which the fibroblasts were harvested. These divergent phenotypes occur regardless of the drug tested and result from modulation of apoptotic priming within tumor cells. Our study highlights unexpected diversity in tumor-stroma interactions, and we reveal new principles that dictate how fibroblasts alter tumor drug responses.
Mol Syst Biol. 2018 Aug 6;14(8):e8322. doi: 10.15252/msb.20188322.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/49863
Rights© 2018 The Authors. Published under the terms of the CC BY 4.0 license.
Except where otherwise noted, this item's license is described as © 2018 The Authors. Published under the terms of the CC BY 4.0 license.