title: Aquaporin-4 in glioma and metastatic tissues harboring 5-aminolevulinic acid-induced porphyrin fluorescence.
abstract: BACKGROUND
  Aquaporin channels (AQPs) are a group of integral membrane proteins that regulate the transport of water through cell membranes. Previous studies have shown that up-regulation of AQP1 and AQP4, two of the predominant AQPs in the human brain, in high grade glial tumors contribute to cerebral edema. Others link AQPs to the regulation of human glioma cell migration and invasion. The aim of this study was to determine AQPs expression in tumor tissue harboring 5-aminolevulinic acid (ALA)-induced porphyrin fluorescence with flow cytometry and compare it to the expression in normal brain tissue.
  
  
  METHODS
  Tissue samples were obtained from fluorescing brain tumors of 26 patients treated with ALA prior to surgery (20 mg/kg b.w.). Expression levels of aquaporin channels were measured in primary tissue cultures using a FACS CANTO I flow cytometer. A control group consisted of four non-fluorescing tissue samples, the C6 and the U87 cell line.
  
  
  RESULTS
  Nineteen gliomas (14 high grade, 5 low grade) and 7 metastases were analyzed. On the 4th post-operative day, expression levels of AQP4 channels, but not of AQP1 channels, were significantly increased in samples from fluorescing tissue compared to non-fluorescing tissue. In addition we could see how ALA induces fluorescence in metastases.
  
  
  CONCLUSIONS
  Flow cytometry appears to be an auspicious method for the analysis of porphyrins and AQPs in primary brain cell tumor cultures. ALA fluorescing tissue showed higher AQP4 expression compared to normal brain tissue. The demonstrated expression in a context with ALA could open a targeted therapeutic spectrum, for example to selectively target AQP4.
authors.affiliation: Department of Neurosurgery, University Hospital of Münster, Münster, Germany. Electronic address: eric.suero@ukmuenster.de.
authors.forename: Eric Jose
authors.initials: EJ
authors.lastname: Suero Molina
authors.forename: Hilko
authors.initials: H
authors.lastname: Ardon
authors.forename: Juliane
authors.initials: J
authors.lastname: Schroeteler
authors.forename: Mark
authors.initials: M
authors.lastname: Klingenhöfer
authors.forename: Markus
authors.initials: M
authors.lastname: Holling
authors.forename: Johannes
authors.initials: J
authors.lastname: Wölfer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fischer
authors.forename: Walter
authors.initials: W
authors.lastname: Stummer
authors.forename: Christian
authors.initials: C
authors.lastname: Ewelt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005453:Fluorescence; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000378:metabolism*; D061251:Primary Cell Culture; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D017319:Photosensitizing Agents; D011166:Porphyrins; D051398:Aquaporin 1; D000622:Aminolevulinic Acid
keywords: 5-Aminolaevulinic acid; Aquaporin-1; Aquaporin-4; Glioblastoma multiforme; Metastasis