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Series GSE80333 Query DataSets for GSE80333
Status Public on Sep 28, 2016
Title Spatial proximity to fibroblasts impacts molecular features and therapeutic sensitivity of breast cancer cells influencing clinical outcomes
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Using a 3D co-culture model, we identified significant sub-type-specific changes in the gene expression, metabolic, and therapeutic sensitivity profiles of breast cancer cells in contact with cancer-associated fibroblasts (CAFs). CAF-induced gene expression signatures predicted clinical outcome and immune-related differences in the microenvironment. We found that CAFs strongly protect carcinoma cells from lapatinib, attributable to its reduced accumulation in carcinoma cells and an elevated apoptotic threshold. Using synthetic lethality approaches, we identified molecular pathways whose inhibition sensitizes HER2+ breast cancer cells to lapatinib both in vitro and in vivo including JAK2/STAT3 and hyaluronic acid. Neoadjuvant lapatinib therapy in HER2+ breast tumors lead to a significant increase of phospho-STAT3+ cancer cells and a decrease in the spatial proximity of proliferating (Ki67+) cells to CAFs impacting therapeutic responses. Our studies identify CAF-induced physiologically and clinically relevant changes in cancer cells and offer novel approaches for overcoming microenvironment-mediated therapeutic resistance.
Overall design SAGE-Seq: Differential expression analysis of five different cell lines (MCF10DCIS, SUM149PT, MCF7, T47D, and MDA-MB-453) representing three different breast cancer sub-types (triple-negative, luminal estrogen receptor positive, and HER2 positive) that were cultured in the presence and absence of cancer-associated fibroblasts (CAFs).
RNA-Seq: Differential expression analysis of stromal fibroblast cells from different origins (primary breast tumors, normal breast tissue, and brain metastases of breast cancer).
Contributor(s) Ekram MB, Marusyk A, Tabassum DP, Polyak K
Citation(s) 27671678
Submission date Apr 15, 2016
Last update date May 15, 2019
Contact name Muhammad B Ekram
Organization name Dana-Farber Cancer Institute
Department Medical Oncology
Lab Kornelia Polyak Lab
Street address 450 Brookline Avenue, DA 740A
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (23)
GSM2124695 MCF7_separate_culture
GSM2124696 MCF7_co-culture
GSM2124697 T47D_separate_culture
BioProject PRJNA318622
SRA SRP073375

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Supplementary file Size Download File type/resource
GSE80333_epithelial_SAGE-Seq_counts_table.tsv.gz 297.6 Kb (ftp)(http) TSV
GSE80333_fibroblast_RNA-Seq_counts_table.tsv.gz 415.8 Kb (ftp)(http) TSV
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