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Status |
Public on Apr 24, 2024 |
Title |
Cancer-stromal cell interactions in breast cancer brain metastases induce glycocalyx-mediated resistance to HER2-targeting therapies [RNA-seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
In a 3D coculture with stroma cells derived from breast cancer patients’ brain metastasis, HER2+ breast cancer cells were protected from HER2-targeted therapies, particularly the EGFR/HER2 small molecule inhibitor neratinib. To get insight into how this protection arises, a Synthetic Notch (SynNotch) reporter model allowed to study the effect of direct contact between stroma and cancer cells.
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Overall design |
To identify stroma-contact specific changes, a SynNotch reporter was used with breast cancer cell lines constitutively expressing mCherry and transiently expressing BFP when in direct contact with BM3 cells engineered with cell surface GFP. Following coculture of organoids in 3D with or without neratinib, cells were dissociated and sorted by Fluorescence-activated cell sorting (FACS) for mCherry+BFP- (breast cancer, non-contact) and mCherry+BFP+ (DP breast cancer, stroma-contact) fractions
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Contributor(s) |
Polyak K, Goyette M, Stevens L |
Citation(s) |
38709925 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
P50 CA168504 |
Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer |
DANA-FARBER CANCER INSTITUTE |
Kornelia Polyak |
R35 CA197623 |
Targeting intratumor heterogeneity in breast cancer |
DANA-FARBER CANCER INSTITUTE |
Kornelia Polyak |
R01 CA200423 |
Chemical Glycoproteomics |
STANFORD UNIVERSITY |
Carolyn Bertozzi |
T32 CA236754 |
Cancer Chemical Biology and Metabolism Training Program |
DANA-FARBER CANCER INSTITUTE |
Nika N Danial |
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Submission date |
Dec 07, 2023 |
Last update date |
May 31, 2024 |
Contact name |
Kornelia Polyak |
E-mail(s) |
kornelia_polyak@dfci.harvard.edu
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Phone |
617-632-2106
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Organization name |
Dana-Farber Cancer Institute
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Department |
Medical Oncology
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Lab |
Polyak
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Street address |
450 Brookline Ave
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City |
Boston |
State/province |
MA |
ZIP/Postal code |
02215 |
Country |
USA |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (40)
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This SubSeries is part of SuperSeries: |
GSE249574 |
Cancer-stromal cell interactions in breast cancer brain metastases induce glycocalyx-mediated resistance to HER2-targeting therapies |
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Relations |
BioProject |
PRJNA1049737 |