title: Modulation of migratory activity and invasiveness of human glioma spheroids following 5-aminolevulinic acid-based photodynamic treatment. Laboratory investigation.
abstract: OBJECTIVE
  Five-aminolevulinic acid-mediated photodynamic therapy (ALA/PDT) can improve the clinical outcome in patients suffering from glioblastoma. Besides direct phototoxicity, additional mechanisms may contribute. Therefore, the authors studied the influence of ALA/PDT on glioblastoma's migratory and invasive behavior in a human glioma cell spheroid model.
  
  
  METHODS
  Glioma spheroids were grown from human U373 and A172 cell lines. After ALA/PDT of spheroids, the authors assessed the migration of tumor cells and their capacity to invade a collagen matrix, as well as changes in their viability, morphology, and expression of matrix metalloproteinases (MMPs).
  
  
  RESULTS
  The authors found that ALA/PDT caused long-lasting, nearly complete suppression of glioma cell migration and matrix invasion compared with nontherapeutic controls, including either irradiation or incubation with ALA only. Although ALA/PDT induced tumor cell apoptosis, suppression of migration/invasion was not simply due to phototoxicity because 50% of tumor cells remained vital throughout the observation period. Moreover, the morphology of ALA/PDT-treated cells changed significantly toward a polygonal, epithelial-like appearance, which was associated with alterations in the actin cytoskeleton. Furthermore, downregulation of MMP-7 and -8 was observed after treatment whereas other MMPs remained unchanged.
  
  
  CONCLUSIONS
  In addition to directly eliminating glioma cells through apoptosis, ALA/PDT alters their invasiveness, possibly due to the effects on the cytoskeletal organization and MMP expression.
authors.affiliation: Department of Neurosurgery, Heinrich-Heine-University, Düsseldorf, Germany. etminan@uni-duesseldorf.de
authors.forename: Nima
authors.initials: N
authors.lastname: Etminan
authors.forename: Corinna
authors.initials: C
authors.lastname: Peters
authors.forename: Julian
authors.initials: J
authors.lastname: Ficnar
authors.forename: Suzan
authors.initials: S
authors.lastname: Anlasik
authors.forename: Erich
authors.initials: E
authors.lastname: Bünemann
authors.forename: Philipp J
authors.initials: PJ
authors.lastname: Slotty
authors.forename: Daniel
authors.initials: D
authors.lastname: Hänggi
authors.forename: Hans-Jakob
authors.initials: HJ
authors.lastname: Steiger
authors.forename: Rüdiger V
authors.initials: RV
authors.lastname: Sorg
authors.forename: Walter
authors.initials: W
authors.lastname: Stummer
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D010778:Photochemotherapy; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000622:Aminolevulinic Acid