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The CXCR4-CXCL12 axis in Ewing sarcoma: promotion of tumor growth rather than metastatic disease.


ABSTRACT:

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Background

Chemokine receptor CXCR4, together with its ligand CXCL12, plays critical roles in cancer progression, including growth, metastasis and angiogenesis. Ewing sarcoma is a sarcoma with poor prognosis despite current therapies, particularly for patients with advanced-stage disease. Lungs and bone (marrow), organs of predilection for (primary/metastatic) Ewing sarcoma, represent predominant CXCL12 sources.

Methods

To gain insight into the role of the CXCR4-CXCL12 axis in Ewing sarcoma, CXCR4, CXCL12 and hypoxia-inducible factor-1? protein expression was studied in therapy-naïve and metastatic tumors by immunohistochemistry. CXCR4 function was assessed in vitro, by flow cytometry and proliferation/ cell viability assays, in the presence of recombinant CXCL12 and/or CXCR4-antagonist AMD3100 or under hypoxic conditions.

Results

Whereas CXCR4 was predominantly expressed by tumor cells, CXCL12 was observed in both tumor and stromal areas. Survival analysis revealed an (expression level-dependent) negative impact of CXCR4 expression (p?ConclusionsTogether, our results imply a crucial role for the CXCR4-CXCL12 axis in auto- and/or paracrine growth stimulation. Integration of CXCR4-targeting strategies into first- and/or second-line treatment regimens may represent a promising treatment option for Ewing sarcoma.

SUBMITTER: Berghuis D 

PROVIDER: S-EPMC3549731 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Publications

The CXCR4-CXCL12 axis in Ewing sarcoma: promotion of tumor growth rather than metastatic disease.

Berghuis Dagmar D   Schilham Marco W MW   Santos Susy J SJ   Savola Suvi S   Knowles Helen J HJ   Dirksen Uta U   Schaefer Karl-Ludwig KL   Vakkila Jukka J   Hogendoorn Pancras Cw PC   Lankester Arjan C AC  

Clinical sarcoma research 20121218 1


<h4>Unlabelled</h4><h4>Background</h4>Chemokine receptor CXCR4, together with its ligand CXCL12, plays critical roles in cancer progression, including growth, metastasis and angiogenesis. Ewing sarcoma is a sarcoma with poor prognosis despite current therapies, particularly for patients with advanced-stage disease. Lungs and bone (marrow), organs of predilection for (primary/metastatic) Ewing sarcoma, represent predominant CXCL12 sources.<h4>Methods</h4>To gain insight into the role of the CXCR4  ...[more]

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