human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: ABSTRACT : 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-1alpha protein expression was studied in therapy-naive 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 &lt ; 0.04 ) . A role for the CXCR4-CXCL12 axis in Ewing sarcoma growth was suggested by our observations that i ) CXCR4 expression correlated positively with tumor volume at diagnosis ( p = 0.013 ) , ii ) CXCL12 was present within the microenvironment of virtually all cases , iii ) CXCL12 induced proliferation of CXCR4-positive Ewing sarcoma cell lines , which could be abrogated by AMD3100 . CXCR4 expression was not correlated with occurrence of metastatic disease . Also , therapy-naive tumors demonstrated higher CXCR4 expression as compared to metastases ( p = 0.027 ) . Evaluation of in vivo hypoxia-inducible factor-1alpha expression and culture of cells under hypoxic conditions revealed no role for hypoxia in CXCR4 expression . CONCLUSIONS : Together , 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 .
    OUTPUT:

agent
activating invasion and metastasis
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: ABSTRACT : 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-1alpha protein expression was studied in therapy-naive 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 &lt ; 0.04 ) . A role for the CXCR4-CXCL12 axis in Ewing sarcoma growth was suggested by our observations that i ) CXCR4 expression correlated positively with tumor volume at diagnosis ( p = 0.013 ) , ii ) CXCL12 was present within the microenvironment of virtually all cases , iii ) CXCL12 induced proliferation of CXCR4-positive Ewing sarcoma cell lines , which could be abrogated by AMD3100 . CXCR4 expression was not correlated with occurrence of metastatic disease . Also , therapy-naive tumors demonstrated higher CXCR4 expression as compared to metastases ( p = 0.027 ) . Evaluation of in vivo hypoxia-inducible factor-1alpha expression and culture of cells under hypoxic conditions revealed no role for hypoxia in CXCR4 expression . CONCLUSIONS : Together , 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 .
    OUTPUT:
