Influence of hypoxia-dependent factors on the progression of neuroblastoma
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Influence of hypoxia-dependent factors on the progression of neuroblastoma. / Ameis, Helen M; Drenckhan, Astrid; Freytag, Morton; Izbicki, Jakob R; Supuran, Claudiu T; Reinshagen, Konrad; Holland-Cunz, Stefan; Gros, Stephanie J.
In: PEDIATR SURG INT, Vol. 32, No. 2, 02.2016, p. 187-92.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Influence of hypoxia-dependent factors on the progression of neuroblastoma
AU - Ameis, Helen M
AU - Drenckhan, Astrid
AU - Freytag, Morton
AU - Izbicki, Jakob R
AU - Supuran, Claudiu T
AU - Reinshagen, Konrad
AU - Holland-Cunz, Stefan
AU - Gros, Stephanie J
PY - 2016/2
Y1 - 2016/2
N2 - PURPOSE: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.
AB - PURPOSE: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.
KW - Anoxia
KW - Antigens, Neoplasm
KW - Biomarkers, Tumor
KW - Carbonic Anhydrases
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Cells, Cultured
KW - Child, Preschool
KW - Disease Progression
KW - Female
KW - Humans
KW - Infant
KW - Kaplan-Meier Estimate
KW - Male
KW - Neuroblastoma
KW - Phosphoglycerate Kinase
KW - Journal Article
U2 - 10.1007/s00383-015-3831-8
DO - 10.1007/s00383-015-3831-8
M3 - SCORING: Journal article
C2 - 26510737
VL - 32
SP - 187
EP - 192
JO - PEDIATR SURG INT
JF - PEDIATR SURG INT
SN - 0179-0358
IS - 2
ER -