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DKK2 maintains osteotropism, invasiveness and metastatic potential in Ewing Tumors

ABSTRACT: Ewing tumors (ET) are osteolytic bone cancers mostly affecting children and young adults, and are characterized by early lung and distant bone metastases. Here we identified the dickkopf 2 homolog (DKK2) as a highly over-expressed gene in ET compared to normal tissues, which is critically involved in ET aggressiveness. Using RNA interference, we show that DKK2 promotes anchorage-independent colony formation and proliferation of ET cells in vitro and tumorigenicity in vivo. Analysis of the invasion potential in vitro and in an orthotopic bone xenotransplantation model revealed a strong correlation of DKK2 expression and ET invasiveness that is possibly mediated by its downstream effector matrix metallopeptidase 1 (MMP1). Gene expression analyses proved DKK2 to differentially regulate genes such as CXCR4, PTHrP, RUNX2 and TGFÎ²1, that are associated with homing, invasion and growth of cancer cells in bone tissue. Moreover, we observed that DKK2 promotes bone infiltration and osteolysis in vivo. Interestingly suppression of DKK2 expression increases neuronal differentiation, but at the same time decreases chondrogenic and osteogenic differentiation of ET cells. These data provide evidence that DKK2 is a key player in ET invasiveness and osteotropism, indicating a critical role of DKK2 for malignancy and the differential phenotype of ET. 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Olivia Prazeres da Costa

PROVIDER: E-GEOD-36100 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Homo sapiens

Project description:DKK2 Mediates Osteolysis, Invasiveness, and Metastatic Spread in Ewing Sarcoma

| PRJNA152971 | ENA

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