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dc.contributor.authorLandry, Benjamin D.
dc.contributor.authorLeete, Thomas
dc.contributor.authorRichards, Ryan
dc.contributor.authorCruz-Gordillo, Peter
dc.contributor.authorSchwartz, Hannah
dc.contributor.authorHoneywell, Megan E
dc.contributor.authorRen, Gary
dc.contributor.authorSchwartz, Alyssa D.
dc.contributor.authorPeyton, Shelly R.
dc.contributor.authorLee, Michael J
dc.date2022-08-11T08:10:59.000
dc.date.accessioned2022-08-23T17:27:26Z
dc.date.available2022-08-23T17:27:26Z
dc.date.issued2018-08-06
dc.date.submitted2018-09-19
dc.identifier.citation<p>Mol Syst Biol. 2018 Aug 6;14(8):e8322. doi: 10.15252/msb.20188322.</p>
dc.identifier.issn1744-4292 (Linking)
dc.identifier.doi10.15252/msb.20188322
dc.identifier.pmid30082272
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49863
dc.description.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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30082272&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© 2018 The Authors. Published under the terms of the CC BY 4.0 license.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectDrug sensitivity
dc.subjectprecision medicine
dc.subjecttriple‐negative breast cancer
dc.subjecttumor microenvironment
dc.subjecttumor–stroma interaction
dc.subjectBiochemistry
dc.subjectCancer Biology
dc.subjectCell Biology
dc.subjectGenetics and Genomics
dc.subjectMolecular Biology
dc.subjectSystems Biology
dc.titleTumor-stroma interactions differentially alter drug sensitivity based on the origin of stromal cells
dc.typeJournal Article
dc.source.journaltitleMolecular systems biology
dc.source.volume14
dc.source.issue8
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1134&amp;context=sysbio_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/sysbio_pubs/135
dc.identifier.contextkey12900759
refterms.dateFOA2022-08-23T17:27:27Z
html.description.abstract<p>Due 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.</p>
dc.identifier.submissionpathsysbio_pubs/135
dc.contributor.departmentDepartment of Molecular, Cell and Cancer Biology
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentProgram in Systems Biology
dc.source.pagese8322


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© 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.