Influence of hypoxia-dependent factors on the progression of neuroblastoma

被引:13
作者
Ameis, Helen M. [1 ]
Drenckhan, Astrid [2 ]
Freytag, Morton [2 ]
Izbicki, Jakob R. [2 ]
Supuran, Claudiu T. [3 ]
Reinshagen, Konrad [1 ]
Holland-Cunz, Stefan [4 ]
Gros, Stephanie J. [2 ,4 ]
机构
[1] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Surg, Altona Childrens Hosp, Hamburg, Germany
[2] Univ Med Ctr Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, Martinistr 52, D-20246 Hamburg, Germany
[3] Univ Florence, Sez Sci Farmaceut, Dept Neurofarba, Florence, Italy
[4] Univ Childrens Hosp Basel, Dept Pediat Surg, Spitalstr 33, CH-4031 Basel, Switzerland
关键词
Hypoxia; CAIX; PGK1; Neuroblastoma; Tumour microenvironment; CARBONIC-ANHYDRASE-IX; SQUAMOUS-CELL CARCINOMA; TUMOR HYPOXIA; INTRACELLULAR PH; CANCER; EXPRESSION; PROGNOSIS; THERAPY; BREAST; MICROENVIRONMENT;
D O I
10.1007/s00383-015-3831-8
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Several oxygen-dependent factors, e.g., CAIX (carbonic anhydrase IX) or phosphoglycerate kinase 1 (PGK1) interacting with the CXCR4/SDF1 axis (chemokine receptor 4/stromal cell derived factor 1) have been shown to be involved in processes of tumour pathology including tumourigenicity, tumour cell dissemination and poor survival in several solid tumour entities. The aim of the current study was to evaluate the influence of the hypoxia-inducible factors CAIX and PGK1 on progression of neuroblastoma and to evaluate the clinical relevance of possible therapeutic approaches. Expression of hypoxia-dependent factors PGK1 and CAIX was examined in neuroblastoma specimen, was correlated with clinical parameters, and was studied in neuroblastoma cells. The impact of these hypoxic factors was evaluated by proliferation assays under targeted therapy. Expression of hypoxia-dependent factors was found in 50 % of neuroblastoma specimen. In neuroblastoma cells, CAIX and PGK1 expression is up regulated under hypoxia and correlates with response to targeted anti-proliferative treatment. The negative impact on survival, although significant for both CAIX and PGk1, appears to be stronger for CAIX. Our results show that the hypoxic factors in the tumour`s microenvironment further the progression of tumour disease. This strengthens the perspectives for additive novel therapeutic approaches targeting hypoxia-dependent factors in this childhood disease.
引用
收藏
页码:187 / 192
页数:6
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