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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 01, 2010 |
| Title |
Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Carcinoma-associated fibroblasts (CAFs) that express α-smooth-muscle-actin (αSMA+) contribute to cancer progression, but their precise origin and role in tumorigenesis is not established. Using mouse models of inflammation-induced gastric cancer, we show that at least 20% of CAFs originate from bone marrow and derive from mesenchymal stem cells (MSCs). Surprisingly, we find that αSMA+ myofibroblasts (MF) are niche cells normally present in bone marrow and increase markedly in the bone marrow and blood during progression to dysplasia. MSC-derived CAFs that are recruited to the dysplastic stomach express IL-6, Wnt5α and BMP4 and show DNA hypomethylation. Bone marrow (BM)-derived CAFs strongly promote tumor growth in organotypic and xenograft models. In addition, CAFs are generated from MSCs and are recruited to distant tumor sites in a TGF-β- and SDF-1α-dependent manner. Carcinogenesis therefore involves the expansion and relocation of normal bone marrow niche cells to the tumor site where they create a new niche to sustain cancer progression.
Since resident (non-BM-derived) CAFs could not be cultured and directly compared to BM-derived CAFs, we additionally isolated total RFP(+) gastric CAFs from aSMA-RFP mice with Helicobacter felis-induced dysplasia, and compared them to GFP(+) BM-derived gastric CAFs from mice with H. felis-induced dysplasia mice that had been transplanted with UBC-EGFP bone marrow. The RFP+ CAFs (HF CAF) represent total CAFs (of which only 20% were BM-derived), while the latter represented only BM-derived CAFs (BM CAF). We compared their gene expression using the Illumina array (MouseWG-6v2) directly after FACS sorting. Interestingly, the GFP+ BM-derived CAFs expressed higher levels of inflammatory genes (IL-6, IL-1β, IL-33) and a number of tumor and stem cell associated factors (CCL5, SPP1, Notch3, MMP9, CD47, CXCR4, PARP10,) compared to the total (RFP+) population of gastric CAFs.
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| Overall design |
Comparison of bone marrow-derived GFP-labeled gastric CAFs versus all gastric CAFs.
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| Contributor(s) |
Quante M, Tu SP, Tomita H, Gonda T, Wang SS, Takashi S, Baik GH, Shibata W, DiPrete B, Betz KS, Friedman R, Varro A, Tycko B, Wang TC |
| Citation(s) |
21316604 |
| Submission date |
Aug 10, 2010 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Michael Quante |
| E-mail(s) |
mq2140@columbia.edu
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| Organization name |
Columbia University Medical Center
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| Department |
Digestive and Liver Disease
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| Lab |
Wang, Timothy
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| Street address |
1130 St. Nicholas Av
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA131823 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23548_RAW.tar |
15.8 Mb |
(http)(custom) |
TAR |
| GSE23548_non-normalized.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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