OncoRay--National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e515-23. doi: 10.1016/j.ijrobp.2012.06.012. Epub 2012 Aug 15.
Cell invasion represents one of the major determinants that treatment has failed for patients suffering from glioblastoma. Contrary findings have been reported for cell migration upon exposure to ionizing radiation. Here, the migration and invasion capability of glioblastoma cells on and in collagen type I were evaluated upon irradiation with X-rays or carbon ions.
Migration on and invasion in collagen type I were evaluated in four established human glioblastoma cell lines exposed to either X-rays or carbon ions. Furthermore, clonogenic radiation survival, proliferation (5-bromo-2-deoxyuridine positivity), DNA double-strand breaks (γH2AX/53BP1-positive foci), and expression of invasion-relevant proteins (eg, β1 integrin, FAK, MMP2, and MMP9) were explored. Migration and invasion assays for primary glioblastoma cells also were carried out with X-ray irradiation.
Neither X-ray nor carbon ion irradiation affected glioblastoma cell migration and invasion, a finding similarly observed in primary glioblastoma cells. Intriguingly, irradiated cells migrated unhampered, despite DNA double-strand breaks and reduced proliferation. Clonogenic radiation survival was increased when cells had contact with extracellular matrix. Specific inhibition of the β1 integrin or proliferation-associated signaling molecules revealed a critical function of JNK, PI3K, and p38 MAPK in glioblastoma cell invasion.
These findings indicate that X-rays and carbon ion irradiation effectively reduce proliferation and clonogenic survival without modifying the migration and invasion ability of glioblastoma cells in a collagen type I environment. Addition of targeted agents against members of the MAPK and PI3K signaling axis to conventional chemoradiation therapy seems potentially useful to optimize glioblastoma therapy.
细胞侵袭是胶质母细胞瘤患者治疗失败的主要决定因素之一。然而，有研究报道称，细胞在接受电离辐射后会发生迁移。本研究旨在评估 X 射线或碳离子照射后，胶质母细胞瘤细胞在Ⅰ型胶原上的迁移和侵袭能力。
在四种已建立的人胶质母细胞瘤细胞系中，评估其在Ⅰ型胶原上的迁移和侵袭能力，分别用 X 射线或碳离子照射。此外，还探索了克隆形成辐射存活、增殖（5-溴-2-脱氧尿嘧啶阳性）、DNA 双链断裂（γH2AX/53BP1 阳性焦点）以及侵袭相关蛋白（如β1 整合素、FAK、MMP2 和 MMP9）的表达。还进行了 X 射线照射下原代胶质母细胞瘤细胞的迁移和侵袭实验。
X 射线和碳离子照射均未影响胶质母细胞瘤细胞的迁移和侵袭，这一发现同样适用于原代胶质母细胞瘤细胞。有趣的是，尽管存在 DNA 双链断裂和增殖减少，照射后的细胞仍能无障碍迁移。当细胞与细胞外基质接触时，克隆形成辐射存活增加。β1 整合素或增殖相关信号分子的特异性抑制表明，JNK、PI3K 和 p38 MAPK 在胶质母细胞瘤细胞侵袭中具有关键作用。
这些发现表明，X 射线和碳离子照射可有效降低增殖和克隆形成存活，而不会改变胶质母细胞瘤细胞在Ⅰ型胶原环境中的迁移和侵袭能力。在传统放化疗的基础上添加针对 MAPK 和 PI3K 信号通路成员的靶向药物，可能有助于优化胶质母细胞瘤的治疗。
