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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 17, 2020 |
| Title |
Transcriptomic profiling of MDA-MD-231 and MDA-MB-231-LM1 cells isolated from mouse lungs at micrometastatic stage |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Cancer-associated fibroblasts promote the development of many primary malignancies, but their function in metastatic progression is poorly understood. Here, we demonstrate that colonization of the lungs by metastatic breast cancer cells induces an inflammatory phenotype in lung fibroblasts. CXCL9 and CXCL10 are induced in an NFκB-dependent manner in metastasis-associated fibroblasts in response IL-1α and IL-1β secreted by disseminated breast cancer cells. We find that the chemokine receptor CXCR3, that binds CXCL9/10, is expressed in a small subset of breast cancer cells that exhibits greater tumor-initiating ability when co-transplanted with fibroblasts. CXCR3-expressing cancer cells maintain JNK signaling that drives IL-1A/B expression, and thus rendering this subpopulation efficient in both inducing CXCL9/10 in lung fibroblasts and responding to the chemokines. Importantly, disruption of the CXCL9/10-CXCR3 axis significantly reduces metastatic colonization in xenograft and syngeneic mouse models suggesting an essential role of this paracrine crosstalk in metastatic progression and a potential therapeutic vulnerability for the treatment of metastatic breast cancer.
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| Overall design |
For profiling of MDA-MB-231 (MDA) and MDA-MB-231-LM2 (MDA-LM2) breast cancer cells at a micrometastatic stage of lung colonization, NSG mice (6-8 weeks of age) were injected via the tail vein with MDA or highly metastatic MDA-LM2 breast cancer cells carrying a triple reporter expressing the genes herpes simplex virus thymidine kinase 1, green fluorescent proteins (GFP), and firefly luciferase, thus enabling bioluminescent imaging of lung metastatic progression. At week 1 post cancer cell injection (representing micrometastatic stage), lungs from mice with similar metastatic burden were harvested. Cancer cells were isolated from by fluorescence-activated cell sorting (FACS) based on GFP. Three biological replicates were analyzed.
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| Contributor(s) |
Pein M, Oskarsson T |
| Citation(s) |
32198421 |
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| Submission date |
Oct 29, 2018 |
| Last update date |
Mar 30, 2020 |
| Contact name |
Maren Pein |
| E-mail(s) |
m.pein@dkfz-heidelberg.de
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| Organization name |
German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)
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| Department |
Junior Research Group Metastatic Niches
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| Lab |
Thordur Oskarsson
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| Street address |
Im Neuenheimer Feld 280
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| City |
Heidelberg |
| State/province |
Baden-Württemberg |
| ZIP/Postal code |
69120 |
| Country |
Germany |
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| Platforms (1) |
| GPL25741 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [CDF: hta20_Hs_ENTREZG, Brainarray version 18.0.0] |
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| Samples (6)
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| GSM3450348 |
MDA, micrometastatic lung, biological rep1 |
| GSM3450349 |
MDA, micrometastatic lung, biological rep2 |
| GSM3450350 |
MDA, micrometastatic lung, biological rep3 |
| GSM3450351 |
MDA-LM2, micrometastatic lung, biological rep1 |
| GSM3450352 |
MDA-LM2, micrometastatic lung, biological rep2 |
| GSM3450353 |
MDA-LM2, micrometastatic lung, biological rep3 |
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| This SubSeries is part of SuperSeries: |
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| Relations |
| BioProject |
PRJNA499115 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE121944_RAW.tar |
250.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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