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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 04, 2011 |
| Title |
PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The platelet-derived growth factor (PDGF) signaling system contributes to tumor angiogenesis and vascular remodeling. Here, we show PDGF-BB markedly induces erythropoietin (EPO) mRNA and protein expression by targeting the PDGFR-beta+ stromal and perivascular compartments. In mouse tumor models, PDGF-BB-induced EPO promotes tumor growth via two mechanisms: 1) paracrine stimulation of tumor angiogenesis by directly inducing endothelial cell proliferation, migration, sprouting and tube formation; and 2) endocrine stimulation of extramedullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. Similarly, delivery of an adenovirus-PDGF-BB to tumor-free mice markedly increases EPO production and hematopoietic parameters. An EPO blockade specifically attenuates PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. At the molecular level, we show that the PDGF-BB-PDGFR-beta signaling system activates EPO promoter via in part transcriptional regulation of ATF3 by possible association with c-Jun and SP1. These findings uncover a novel mechanism of PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis.
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| Overall design |
Comparison of S17 stromal cells treated with PDGF-BB for 72h to control
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| Contributor(s) |
Larsson O, Cao Y |
| Citation(s) |
22138754, 27608497 |
| Submission date |
Nov 15, 2011 |
| Last update date |
Nov 08, 2016 |
| Contact name |
Ola Larsson |
| E-mail(s) |
ola.larsson@ki.se
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| Phone |
+46 (0)8 517 73280
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| Organization name |
Karolinska Institutet
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| Department |
Department of oncology-pathology
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| Street address |
CCK, R8:01
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| City |
Stockholm |
| ZIP/Postal code |
171 76 |
| Country |
Sweden |
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| Platforms (1) |
| GPL7546 |
Affymetrix GeneChip Mouse Genome 430 2.0 Array [CDF: Mm_ENTREZG_10] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA148461 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33717_RAW.tar |
26.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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