期刊
JOURNAL OF NEUROSURGERY
卷 115, 期 2, 页码 281-288出版社
AMER ASSOC NEUROLOGICAL SURGEONS
DOI: 10.3171/2011.3.JNS10434
关键词
aminolevulinic acid; glioma; photodynamic therapy; invasion; migration; oncology
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. (DOI: 10.3171/2011.3.JNS10434)
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