PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Hauer, K.* ; Calzada-Wack, J. ; Steiger, K. ; Grunewald, T.G.* ; Baumhoer, D.* ; Plehm, S.* ; Buch, T.* ; Prazeres da Costa, O.* ; Esposito, I. ; Burdach, S.* ; Richter, G.H.*

DKK2 mediates osteolysis, invasiveness and metastatic spread in Ewing sarcoma.

Cancer Res. 73, 967-977 (2013)
Verlagsversion Volltext DOI PMC
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Ewing sarcoma (ES), 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 ES compared to corresponding normal tissues. Using RNA interference, we demonstrated 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 ES invasiveness that may be mediated by the DKK effector matrix metalloproteinase 1 (MMP1). Further, gene expression analyses established the ability of DKK2 to differentially regulate genes such as CXCR4, PTHrP, RUNX2 and TGFβ1, that are associated with homing, invasion and growth of cancer cells in bone tissue as well as genes important for osteolysis, including HIF1α, 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 ES 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 ES invasion and osteolysis and also in the differential phenotype of ES cells.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
7.856
2.017
46
51
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter DKK2; osteolysis; invasiveness; metastasis; Ewing sarcoma; Wnt Signaling Pathway ; Osteoblast Differentiation ; Breast-cancer ; Bone Metastases ; Molecular Pathogenesis ; Tumor-cells ; Expression ; Protein ; Gene ; Antagonist
Sprache englisch
Veröffentlichungsjahr 2013
Prepublished im Jahr 2012
HGF-Berichtsjahr 2012
ISSN (print) / ISBN 0008-5472
e-ISSN 1538-7445
Zeitschrift Cancer Research
Quellenangaben Band: 73, Heft: 2, Seiten: 967-977 Artikelnummer: , Supplement: ,
Verlag American Association for Cancer Research (AACR)
Verlagsort Philadelphia, Pa.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pathology (PATH)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-500300-001
PubMed ID 23204234
DOI 10.1158/0008-5472.CAN-12-1492
WOS ID WOS:000313739500054
Scopus ID 84872537847
Erfassungsdatum 2012-12-31
[➜Korrektur melden]