Modulation of migratory activity and invasiveness of human glioma spheroids following 5-aminolevulinic acid-based photodynamic treatment: Laboratory investigation

• Published in: Journal of neurosurgery Vol. 115; no. 2; pp. 281 - 288
• Main Authors: ETMINAN, Nima, PETERS, Corinna, FICNAR, Julian, ANLASIK, Suzan, BÜNEMANN, Erich, SLOTTY, Philipp J, HÄNGGI, Daniel, STEIGER, Hans-Jakob, SORG, Rüdiger V, STUMMER, Walter
• Format: Journal Article
• Language: English
• Published: Charlottesville, VA American Association of Neurological Surgeons 01-08-2011
• Subjects: Aminolevulinic Acid - pharmacology; Aminolevulinic Acid - therapeutic use; Biological and medical sciences; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Cell Line, Tumor; Cell Movement - drug effects; Cell Survival - drug effects; Glioma - drug therapy; Glioma - metabolism; Humans; Medical sciences; Neurosurgery; Photochemotherapy; Spheroids, Cellular - drug effects; Spheroids, Cellular - metabolism; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tumor Cells, Cultured; Human; Nervous system diseases; Photodynamic therapy; Spheroid; Invasion; oncology; Treatment; Glioma; Laboratory investigations; Central nervous system disease; aminolevulinic acid; migration; Tumor
• ISSN: 0022-3085; 1933-0693
• DOI: 10.3171/2011.3.JNS10434

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.
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).
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.
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.