Simon Florian, Dittmar Jan-Oliver, Brons Stephan, Orschiedt Lena, Urbschat Steffi, Weber Klaus-Josef, Debus Jürgen, Combs Stephanie E, Rieken Stefan
Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany,
Strahlenther Onkol. 2015 Apr;191(4):347-55. doi: 10.1007/s00066-014-0778-y. Epub 2014 Dec 2.
Sublethal doses of photon irradiation (IR) are suspected to increase tumor cell migration and support locoregional recurrence of disease, which has already been shown in other cell lines. This manuscript describes the effect of photon and carbon-ion IR on WHO class I meningioma cell migration and provides an approach to the underlying cellular mechanisms.
Meningioma cells were gained operatively at the university hospital in Homburg/Saar, Germany. For migration, membranes (8-µm pore sizes) were coated with collagen I, with collagen IV, and with fibronectin. Cells were analyzed in migration experiments with or without serum stimulation, with or without photon and carbon IR 24 h prior to experiments, and with or without integrin antibodies. Fluorescence-activated cell sorting (FACS) analyses of the integrins ανβ1, ανβ3, and ανβ5 were performed without IR and 6, 12 and 24 h after IR. Enzyme-linked immunosorbent assay (ELISA) analyses of matrix metalloproteinases (MMP)-2 and MMP-9 were realized with and without IR after cells were cultured on collagen I, collagen IV, or fibronectin for 24 h. Cells and supernatants for FACS and ELISA were stored at - 18 °C. The significance level was set at 5 % using both Student's t test and two-way ANOVA.
Migration of meningioma cells was serum-inducible (p < 0.001). It could be increased by photon IR (p < 0.02). The integrins ανβ1 and ανβ5 showed a 21 and 11 % higher expression after serum stimulation (not significant), respectively, and ανβ1 expression was raised by 14 % (p = 0.0057) after photon IR. Antibody blockage of the integrins ανβ1 and ανβ5 inhibited serum- and photon-induced migration. Expression of MMP-2 and MMP-9 remained unchanged after both IR and fetal bovine serum (FBS). Carbon-ion IR left both integrin expression and meningioma cell migration unaffected.
Photon but not carbon-ion IR promotes serum-based meningioma cell migration. Fibronectin receptor integrin ανβ1 signaling can be identified as an important mechanism for serum- and photon-induced migration of WHO class I meningioma cells.
亚致死剂量的光子辐射（IR）被怀疑会增加肿瘤细胞迁移并促进疾病的局部复发，这在其他细胞系中已有报道。本手稿描述了光子和碳离子辐射对世界卫生组织I级脑膜瘤细胞迁移的影响，并探讨了其潜在的细胞机制。
脑膜瘤细胞取自德国洪堡/萨尔大学医院的手术标本。对于迁移实验，将孔径为8μm的膜分别用I型胶原、IV型胶原和纤连蛋白包被。在有或无血清刺激、实验前24小时有或无光子和碳离子辐射以及有或无整合素抗体的情况下对细胞进行迁移分析。在无辐射以及辐射后6、12和24小时对整合素ανβ1、ανβ3和ανβ5进行荧光激活细胞分选（FACS）分析。在细胞于I型胶原、IV型胶原或纤连蛋白上培养24小时后，对有无辐射情况下的基质金属蛋白酶（MMP）-2和MMP-9进行酶联免疫吸附测定（ELISA）分析。用于FACS和ELISA的细胞及上清液保存在-18°C。使用学生t检验和双向方差分析，将显著性水平设定为5%。
脑膜瘤细胞的迁移是血清诱导性的（p<0.001）。光子辐射可使其增加（p<0.02）。整合素ανβ1和ανβ5在血清刺激后表达分别升高21%和11%（无显著性差异），光子辐射后ανβ1表达升高14%（p = 0.0057）。整合素ανβ1和ανβ5的抗体阻断抑制了血清和光子诱导的迁移。辐射和胎牛血清（FBS）后，MMP-2和MMP-9的表达均未改变。碳离子辐射对整合素表达和脑膜瘤细胞迁移均无影响。
光子辐射而非碳离子辐射促进基于血清的脑膜瘤细胞迁移。纤连蛋白受体整合素ανβ1信号传导可被确定为血清和光子诱导的世界卫生组织I级脑膜瘤细胞迁移的重要机制。
