Irradiation differentially affects substratum-dependent survival, adhesion, and invasion of glioblastoma cell lines.
Irradiation differentially affects substratum-dependent survival, adhesion, and invasion of glioblastoma cell lines.
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DOI：
10.1038/sj.bjc.6601429
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发表时间：
2003-12-01
影响因子：
8.8
通讯作者：
van Beuningen, D
中科院分区：
文献类型：
--
作者：
Cordes, N;Hansmeier, B;Beinke, C;Meineke, V;van Beuningen, D
电离辐射对细胞外基质 (ECM) 调节的细胞存活以及粘附和侵袭的影响尚不清楚。特别是，多形性胶质母细胞瘤的侵袭性与肿瘤细胞侵入邻近正常脑组织有关。为了更深入地研究这些影响，四种人胶质母细胞瘤细胞系（A-172、U-138、LN-229 和 LN-18）在纤连蛋白 (FN)、基质胶、BSA 或聚苯乙烯上进行了辐照。这项研究的主要发现包括与聚苯乙烯或 BSA 上辐照的细胞相比，FN 或 Matrigel 上辐照的 A-172 细胞的存活率显着增加，但辐照的 U-138、LN-229 和 LN-18 细胞的存活率没有显着增加。辐射诱导所有四种神经胶质瘤细胞系中功能性 β1- 和 β3- 整合素呈剂量依赖性增加。这种整合素诱导导致细胞对 FN 或 Matrigel 的粘附改善。与 U-138、LN-229 和 LN-18 细胞相反，辐射强烈削弱 A-172 细胞的侵袭。所有细胞系的侵袭均被抗整合素抗体、解整合素 echistatin 和 MMP-2/-9 抑制剂 III 抑制。此外，β1-和β3-整合素调节MMP-2的基础和辐射改变的明胶分解活性。测试的胶质母细胞瘤细胞系显示出对 FN 或 Matrigel 的不同细胞敏感性，这影响了细胞的放射敏感性。四分之三的神经胶质瘤细胞系表现出辐射后不依赖于基质的存活和不受辐射影响的侵袭潜力的组合。 β1- 和 β3- 整合素被确定在生存、粘附、侵袭和 MMP-2 活性中发挥重要的调节作用。对放射抗性和侵袭过程的详细了解可能会提供新的治疗策略，以增强致命性高级星形细胞瘤的细胞杀伤力。
Effects of ionising radiation on extracellular matrix (ECM)-modulated cell survival and on adhesion and invasion are not well understood. In particular, the aggressiveness of glioblastoma multiforme has been associated with tumour cell invasion into adjacent normal brain tissue. To examine these effects in more depth, four human glioblastoma cell lines (A-172, U-138, LN-229 and LN-18) were irradiated on fibronectin (FN), Matrigel, BSA or polystyrene. Major findings of this study include a significantly increased survival of irradiated A-172 but not of irradiated U-138, LN-229, and LN-18 cells on FN or Matrigel compared to cells irradiated on polystyrene or BSA. Irradiation induced a dose-dependent increase in functional β1- and β3-integrins in all four glioma cell lines. This integrin induction caused improved cell adhesion to FN or Matrigel. In contrast to U-138, LN-229 and LN-18 cells, irradiation strongly impaired A-172 cell invasion. Invasion of all cell lines was inhibited by anti-integrin antibodies, the disintegrin echistatin and the MMP-2/-9 inhibitor III. Additionally, β1- and β3-integrins modulated basal and radiation-altered gelatinolytic activity of MMP-2. Tested glioblastoma cell lines showed a differential cellular susceptibility to FN or Matrigel which affected the cellular radiosensitivity. Three out of four glioma cell lines demonstrated a combination of a substratum-independent survival after irradiation and an invasive potential which was not affected by irradiation. β1- and β3-integrins were identified to play a substantial, regulatory role in survival, adhesion, invasion and MMP-2 activity. Detailed insights into radioresistance and invasion processes might offer new therapeutic strategies to enhance cell killing of lethal high-grade astrocytoma.