Rieken Stefan, Rieber Juliane, Brons Stephan, Habermehl Daniel, Rief Harald, Orschiedt Lena, Lindel Katja, Weber Klaus J, Debus Jürgen, Combs Stephanie E
University Hospital of Heidelberg, Department of Radiation Oncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
University Hospital of Heidelberg, Department of Radiation Oncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
J Radiat Res. 2015 May;56(3):430-6. doi: 10.1093/jrr/rru120. Epub 2015 Mar 2.
Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse possible mechanisms underlying the potentially radiation-altered motility in medulloblastoma cells. Medulloblastoma cell lines D425 and Med8A were analyzed in migration and adhesion experiments with and without photon and carbon ion irradiation. Expression of integrins was determined by quantitative FACS analysis. Matrix metalloproteinase concentrations within cell culture supernatants were investigated by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Student's t-test. Both photon and carbon ion irradiation significantly reduced chemotactic medulloblastoma cell transmigration through 8-μm pore size membranes, while simultaneously increasing adherence to fibronectin- and collagen I- and IV-coated surfaces. Correspondingly, both photon and carbon ion irradiation downregulate soluble MMP9 concentrations, while upregulating cell surface expression of proadhesive extracellular matrix protein-binding integrin α5. The observed phenotype of radiation-altered motility is more pronounced following carbon ion than photon irradiation. Both photon and (even more so) carbon ion irradiation are effective in inhibiting medulloblastoma cell migration through downregulation of matrix metalloproteinase 9 and upregulation of proadhesive cell surface integrin α5, which lead to increased cell adherence to extracellular matrix proteins.
光子辐射一直被怀疑会增加肿瘤细胞的运动性并促进疾病的局部复发。本研究旨在分析髓母细胞瘤细胞中潜在的辐射改变运动性的可能机制。在有或无光子和碳离子辐射的情况下，对髓母细胞瘤细胞系D425和Med8A进行迁移和黏附实验分析。通过定量荧光激活细胞分选分析（FACS）测定整合素的表达。通过酶联免疫吸附测定（ELISA）研究细胞培养上清液中基质金属蛋白酶的浓度。使用学生t检验进行统计分析。光子和碳离子辐射均显著降低髓母细胞瘤细胞通过8μm孔径膜的趋化性迁移，同时增加对纤连蛋白、I型和IV型胶原包被表面的黏附。相应地，光子和碳离子辐射均下调可溶性MMP9浓度，同时上调促黏附细胞外基质蛋白结合整合素α5的细胞表面表达。碳离子辐射后观察到的辐射改变运动性的表型比光子辐射更明显。光子和（更明显的是）碳离子辐射通过下调基质金属蛋白酶9和上调促黏附细胞表面整合素α5有效抑制髓母细胞瘤细胞迁移，这导致细胞对细胞外基质蛋白的黏附增加。
