Influence of hypoxia-dependent factors on the progression of neuroblastoma
| Autor: | Stephanie J. Gros, Konrad Reinshagen, Claudiu T. Supuran, Helen M. Ameis, Stefan Holland-Cunz, Jakob R. Izbicki, Astrid Drenckhan, Morton Freytag |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male medicine.medical_treatment Cell Kaplan-Meier Estimate CXCR4 Targeted therapy 03 medical and health sciences Chemokine receptor Neuroblastoma 0302 clinical medicine Antigens Neoplasm Cell Line Tumor medicine Biomarkers Tumor Humans Stromal cell-derived factor 1 Phosphoglycerate kinase 1 education Carbonic Anhydrase IX Hypoxia Cells Cultured Carbonic Anhydrases Cell Proliferation education.field_of_study biology Cell growth business.industry Infant General Medicine medicine.disease Phosphoglycerate Kinase 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Child Preschool Pediatrics Perinatology and Child Health biology.protein Cancer research Disease Progression Surgery Female business |
| Zdroj: | Pediatric surgery international. 32(2) |
| ISSN: | 1437-9813 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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