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Mendeley readers
| Title |
PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells
|
|---|---|
| Published in |
Nature Medicine, December 2011
|
| DOI | 10.1038/nm.2575 |
| Pubmed ID | |
| Authors |
Yuan Xue, Sharon Lim, Yunlong Yang, Zongwei Wang, Lasse Dahl Ejby Jensen, Eva-Maria Hedlund, Patrik Andersson, Masakiyo Sasahara, Ola Larsson, Dagmar Galter, Renhai Cao, Kayoko Hosaka, Yihai Cao |
| Abstract |
The platelet-derived growth factor (PDGF) signaling system contributes to tumor angiogenesis and vascular remodeling. Here we show in mouse tumor models that PDGF-BB induces erythropoietin (EPO) mRNA and protein expression by targeting stromal and perivascular cells that express PDGF receptor-β (PDGFR-β). Tumor-derived PDGF-BB promoted tumor growth, angiogenesis and extramedullary hematopoiesis at least in part through modulation of EPO expression. Moreover, adenoviral delivery of PDGF-BB to tumor-free mice increased both EPO production and erythropoiesis, as well as protecting from irradiation-induced anemia. At the molecular level, we show that the PDGF-BB-PDGFR-bβ signaling system activates the EPO promoter, acting in part through transcriptional regulation by the transcription factor Atf3, possibly through its association with two additional transcription factors, c-Jun and Sp1. Our findings suggest that PDGF-BB-induced EPO promotes tumor growth through two mechanisms: first, paracrine stimulation of tumor angiogenesis by direct induction of endothelial cell proliferation, migration, sprouting and tube formation, and second, endocrine stimulation of extramedullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. |
Mendeley readers
The data shown below were compiled from readership statistics for 158 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 2 | 1% |
| Norway | 1 | <1% |
| Italy | 1 | <1% |
| United Kingdom | 1 | <1% |
| Belgium | 1 | <1% |
| China | 1 | <1% |
| Japan | 1 | <1% |
| United States | 1 | <1% |
| Unknown | 149 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 41 | 26% |
| Researcher | 34 | 22% |
| Student > Master | 23 | 15% |
| Student > Bachelor | 16 | 10% |
| Student > Doctoral Student | 9 | 6% |
| Other | 15 | 9% |
| Unknown | 20 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 49 | 31% |
| Medicine and Dentistry | 42 | 27% |
| Biochemistry, Genetics and Molecular Biology | 18 | 11% |
| Chemistry | 6 | 4% |
| Engineering | 5 | 3% |
| Other | 14 | 9% |
| Unknown | 24 | 15% |