Abstract
Background and AimA close relationship between phosphoglycerate kinase 1 (PGK1) and the CXCR4/SDF1 axis (chemokine receptor 4/stromal cell derived factor 1) has been shown for several cancers. However, the role of PGK1 has not been investigated for neuroblastoma, and PGK1 might be a therapeutic target for this tumor entity. The aim of the current study was to evaluate the role of PGK1 expression in neuroblastoma patients, to determine the impact of PGK1 expression levels on survival, and to correlate PGK1 expression with CXCR4 expression and bone marrow dissemination.Materials and MethodsSamples from 22 patients with neuroblastoma that were surgically treated at the University Medical Center Hamburg-Eppendorf were evaluated for expression of PGK1 and CXCR4 using immunohistochemistry. Results were correlated with clinical parameters, metastases and outcome of patients. Immunocytochemistry, proliferation and expression analysis of CXCR4 and PGK1 were performed in neuroblastoma cell lines.ResultsPGK1 is expressed in neuroblastoma cells. PGK1 expression is significantly positively correlated with CXCR4 expression and tumor dissemination to the bone marrow. Moreover the expression of PGK1 is significantly associated with a negative impact on survival in patients with neuroblastoma. PGK1 is downregulated by inhibition of CXCR4 in neuroblastoma cells.ConclusionPGK1 appears to play an important role for neuroblastoma, predicting survival and tumor dissemination. Further in vivo studies outstanding, it is a candidate target for novel therapeutic strategies.
Highlights
Neuroblastoma arises from sympathetic neuroblast cells derived from the neural crest and is the most frequent solid tumour in childhood outside the central nervous system [1,2]
phosphoglycerate kinase 1 (PGK1) expression is significantly positively correlated with CXCR4 expression and tumor dissemination to the bone marrow
The expression of PGK1 is significantly associated with a negative impact on survival in patients with neuroblastoma
Summary
Neuroblastoma arises from sympathetic neuroblast cells derived from the neural crest and is the most frequent solid tumour in childhood outside the central nervous system [1,2]. The outcome strongly correlates with clinical factors (e.g. age, stage and chromosomal aberrations), but the overall survival of patients suffering from this tumour entity is good [5]. Metastastic dissemination in advanced stages of highly malignant neuroblastoma occurs most frequently to bone marrow, bone, liver, and skin [6,7,8,9,10,11,12]. The role of PGK1 has not been investigated for neuroblastoma, and PGK1 might be a therapeutic target for this tumor entity. The aim of the current study was to evaluate the role of PGK1 expression in neuroblastoma patients, to determine the impact of PGK1 expression levels on survival, and to correlate PGK1 expression with CXCR4 expression and bone marrow dissemination
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