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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 21, 2012 |
| Title |
DKK2 Mediates Osteolysis, Invasiveness, and Metastatic Spread in Ewing Sarcoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Ewing sarcoma, an osteolytic malignancy that mainly affects children and young adults, is characterized
by early metastasis to lung and bone. In this study, we identified the pro-metastatic gene DKK2
as a highly overexpressed gene in Ewing sarcoma compared with corresponding normal tissues. Using RNA
interference, we showed that DKK2 was critical for malignant cell outgrowth in vitro and in an orthotopic
xenograft mouse model in vivo. Analysis of invasion potential in both settings revealed a strong correlation of
DKK2 expression to Ewing sarcoma invasiveness that may be mediated by the DKK effector matrix
metalloproteinase 1 (MMP1). Furthermore, gene expression analyses established the ability of DKK2 to
differentially regulate genes such as CXCR4, PTHrP, RUNX2, and TGFb1 that are associated with homing,
invasion, and growth of cancer cells in bone tissue as well as genes important for osteolysis, including HIF1a,
JAG1, IL6, and VEGF. DKK2 promoted bone infiltration and osteolysis in vivo and further analyses defined
DKK2 as a key factor in osteotropic malignancy. Interestingly, in Ewing sarcoma cells, DKK2 suppression
simultaneously increased the potential for neuronal differentiation while decreasing chondrogenic and
osteogenic differentiation. Our results provide strong evidence that DKK2 is a key player in Ewing
sarcoma invasion and osteolysis and also in the differential phenotype of Ewing sarcoma cells.
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| Overall design |
6 samples (3x A673 cells; 3x SK-N-MC cells); for each cell line one sample was transfected with control non silencing siRNA and one sample with DKK2 siRNA (siDKK2_1) and one sample with ITM2A siRNA (siITM2A_7) as an independent knock down.
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| Contributor(s) |
Hauer K, Calzada-Wack J, Grünewald TG, Plehm S, Esposito I, Buch T, Prazeres da Costa O, Burdach S, Richter GH, Steiger K, Baumhoer D, Esposito I |
| Citation(s) |
23204234 |
| Submission date |
Feb 27, 2012 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Olivia Prazeres da Costa |
| E-mail(s) |
olivia.p.dacosta@googlemail.com
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| Phone |
00498941404149
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| Organization name |
Technische Universität München
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| Department |
Medical Microbiology, Immunology and Hygiene
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| Street address |
Trogerstr. 30
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| City |
München |
| State/province |
Bavaria |
| ZIP/Postal code |
81675 |
| Country |
Germany |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA152971 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE36100_RAW.tar |
22.7 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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