Influence of hypoxia-dependent factors on the progression of neuroblastoma.
OBJECTIVE
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.
Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf/Altona Children's Hospital, Hamburg, Germany.
Helen M
HM
Ameis
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Astrid
A
Drenckhan
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Morton
M
Freytag
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Jakob R
JR
Izbicki
Department Neurofarba, Sezione di Scienze farmaceutiche, University of Florence, Florence, Italy.
Claudiu T
CT
Supuran
Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf/Altona Children's Hospital, Hamburg, Germany.
Konrad
K
Reinshagen
Department of Pediatric Surgery, University Children's Hospital of Basel, Spitalstrasse 33, 4031, Basel, Switzerland.
Stefan
S
Holland-Cunz
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. stephanie.gros@ukbb.ch.|Department of Pediatric Surgery, University Children's Hospital of Basel, Spitalstrasse 33, 4031, Basel, Switzerland. stephanie.gros@ukbb.ch.
Stephanie J
SJ
Gros
D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D000860:Hypoxia; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009447:Neuroblastoma / Q000378:metabolism*; D010735:Phosphoglycerate Kinase / Q000235:genetics* / Q000378:metabolism*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C577282:PGK1 protein, human; D010735:Phosphoglycerate Kinase; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
CAIX; Hypoxia; Neuroblastoma; PGK1; Tumour microenvironment