Modulation of migratory activity and invasiveness of human glioma spheroids following 5-aminolevulinic acid based photodynamic treatment Laboratory investigation
Modulation of migratory activity and invasiveness of human glioma spheroids following 5-aminolevulinic acid based photodynamic treatment Laboratory investigation
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DOI：
10.3171/2011.3.jns10434
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发表时间：
2011-08-01
影响因子：
4.1
通讯作者：
Stummer, Walter
中科院分区：
文献类型：
--
作者：
Etminan, Nima;Peters, Corinna;Stummer, Walter
物体。5-氨基乙酰丙酸介导的光动力疗法(ALA/PDT)可改善胶质母细胞瘤患者的临床预后。除了直接的光毒性外，其他机制也可能起作用。因此，作者在人脑胶质瘤细胞球体模型中研究了ALA/PDT对胶质母细胞瘤迁移和侵袭行为的影响。人脑胶质瘤球体是从人U373和A172细胞系培养出来的。在球体的ALA/PDT后，作者评估了肿瘤细胞的迁移和它们侵袭胶原基质的能力，以及它们的存活率、形态和基质金属蛋白酶(MMPs)的表达的变化。结果。作者发现，与非治疗对照相比，ALA/PDT导致了长期的、几乎完全的抑制胶质瘤细胞迁移和基质侵袭，包括照射或仅与ALA孵育。尽管ALA/PDT可诱导肿瘤细胞的凋亡，但其迁移/侵袭的抑制并不是单纯的光毒性所致，因为在整个观察期内，50%的肿瘤细胞仍然存活。此外，ALA/PDT处理的细胞的形态发生了显著的变化，呈多边形上皮样外观，这与肌动蛋白细胞骨架的变化有关。此外，治疗后可观察到MMP7和MMP8的表达下调，而其他MMPs的表达没有变化。除了通过细胞凋亡直接清除胶质瘤细胞外。ALA/PDT改变其侵袭性，可能与其对细胞骨架组织和基质金属蛋白酶表达的影响有关。(DOI：10.3171/2011.3.JNS10434)
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)