Affiliation:
1. Department of Neurosurgery,
2. Institute for Transplantation Diagnostics and Cell Therapeutics, and
3. Department of Dermatology, Heinrich-Heine-University, Düsseldorf; and
4. Department of Neurosurgery, University of Münster, Germany
Abstract
Object
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.
Publisher
Journal of Neurosurgery Publishing Group (JNSPG)
Subject
Genetics,Animal Science and Zoology
Cited by
43 articles.
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