title: Carbonic anhydrase IX correlates with survival and is a potential therapeutic target for neuroblastoma.
abstract: Carbonic anhydrase IX (CAIX) is involved in pathological processes including tumorgenicity, metastases and poor survival in solid tumors. Twenty-two neuroblastoma samples of patients who were surgically treated at the University Medical Center Hamburg-Eppendorf were evaluated immunohistochemically for expression of CAIX. Results were correlated with clinical parameters and outcome. Neuroblastoma Kelly and SH-EP-Tet-21/N cells were examined for CAIX expression and inhibited with specific inhibitors, FC5-207A and FC8-325A. 32% of neuroblastoma tumors expressed CAIX. This was significantly associated with poorer survival. Kelly and SH-EP-Tet-21/N cells showed a major increase of CAIX RNA under hypoxic conditions. Proliferation of Kelly cells was significantly decreased by CAIX inhibitors, FC5-207A and FC8-325A, while proliferation of SH-EP-Tet-21/N cells was only significantly affected by FC8-325A. CAIX is a potent biomarker that predicts survival in neuroblastoma patients. CAIX-targeted therapy in neuroblastoma cell lines is highly effective and strengthens the potential of CAIX as a clinical therapeutic target in a selected patient collective.
authors.affiliation: a Department of Pediatric Surgery , University Medical Center Hamburg-Eppendorf/Altona Children's Hospital , Hamburg , Germany .
authors.forename: Helen M
authors.initials: HM
authors.lastname: Ameis
authors.affiliation: b Department of General, Visceral and Thoracic Surgery , University Medical Center Hamburg-Eppendorf , Hamburg , Germany .
authors.forename: Astrid
authors.initials: A
authors.lastname: Drenckhan
authors.affiliation: b Department of General, Visceral and Thoracic Surgery , University Medical Center Hamburg-Eppendorf , Hamburg , Germany .
authors.forename: Morton
authors.initials: M
authors.lastname: Freytag
authors.affiliation: b Department of General, Visceral and Thoracic Surgery , University Medical Center Hamburg-Eppendorf , Hamburg , Germany .
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.affiliation: c Department Neurofarba , Sezione di Scienze farmaceutiche, University of Florence , Florence , Italy , and.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.affiliation: a Department of Pediatric Surgery , University Medical Center Hamburg-Eppendorf/Altona Children's Hospital , Hamburg , Germany .
authors.forename: Konrad
authors.initials: K
authors.lastname: Reinshagen
authors.affiliation: d Department of Pediatric Surgery , University Children's Hospital of Basel , Basel , Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Holland-Cunz
authors.affiliation: b Department of General, Visceral and Thoracic Surgery , University Medical Center Hamburg-Eppendorf , Hamburg , Germany .|d Department of Pediatric Surgery , University Children's Hospital of Basel , Basel , Switzerland.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Gros
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015394:Molecular Structure; D009447:Neuroblastoma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D013329:Structure-Activity Relationship; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: Biomarker; CAIX; hypoxia; neuroblastoma; survival