ArticleRadiation oncology (London, England)2015
Sublethal dose of irradiation enhances invasion of malignant glioma cells through p53-MMP 2 pathway in U87MG mouse brain tumor model.
Article in Radiation oncology (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 35 citations in OpenAlex.
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- The Dual Role of Mesenchymal Stem Cells in Cancer Pathophysiology: Pro-Tumorigenic Effects versus Therapeutic Potential.International journal of molecular sciences · 2023Review
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- Molecular Mechanisms and Clinical Challenges of Glioma Invasion.Brain sciences · 2022Review
- Chidamide Inhibits Glioma Cells by Increasing Oxidative Stress via the miRNA-338-5p Regulation of Hedgehog Signaling.Oxidative medicine and cellular longevity · 2020Article
- Radiation Effects on Brain Extracellular Matrix.Frontiers in oncology · 2020Review
- Differential Effects of Ang-2/VEGF-A Inhibiting Antibodies in Combination with Radio- or Chemotherapy in Glioma.Cancers · 2019Article
- Enhancing Radiotherapeutic Effect With Nanoparticle-Mediated Radiosensitizer Delivery Guided By Focused Gamma Rays In Lewis Lung Carcinoma-Bearing Mouse Brain Tumor Models.International journal of nanomedicine · 2019Article
- Molecular and Clinical Insights into the Invasive Capacity of Glioblastoma Cells.Journal of oncology · 2019Review
- Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs.Translational oncology · 2018Article
- Radiation-Induced Transformation of Immunoregulatory Networks in the Tumor Stroma.Frontiers in immunology · 2018Review
- Radiation-Induced Alterations in the Recurrent Glioblastoma Microenvironment: Therapeutic Implications.Frontiers in oncology · 2018Review
- MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53.Oncotarget · 2017Article
- The allosteric AKT inhibitor MK2206 shows a synergistic interaction with chemotherapy and radiotherapy in glioblastoma spheroid cultures.BMC cancer · 2017Article
- Relationship between Glioblastoma Dose Volume Parameters Measured by Dual Time Point Fluoroethylthyrosine-PET and Clinical Outcomes.Frontiers in neurology · 2017Article
- Zinc and zinc-containing biomolecules in childhood brain tumors.Journal of molecular medicine (Berlin, Germany) · 2016Review
- Bevacizumab and radiotherapy for the treatment of glioblastoma: brothers in arms or unholy alliance?Oncotarget · 2016Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlioblastoma is a highly lethal neoplasm that frequently recurs locally after radiotherapy, and most of these recurrences originate from near the irradiated target field. In the present study, we identified the effects of radiation on glioma invasion and p53, TIMP-2, and MMP-2 expression through in vitro and in vivo experiments.
methodsThe U87MG (wt p53) and U251 (mt p53) human malignant glioma cell lines were prepared, and the U2OS (wt 53) and Saos2 (del p53) osteosarcoma cell lines were used as p53 positive and negative controls. The four cell lines and p53 knock-downed U87MG cells received radiation (2-6 Gy) and were analyzed for expression of p53 and TIMP-2 by Western blot, and MMP-2 activity was detected by zymography. In addition, the effects of irradiation on directional invasion of malignant glioma were evaluated by implanting nude mice with bioluminescent u87-Fluc in vivo followed by MMP-2, p53, and TIMP-2 immunohisto-chemistry and in situ zymography.
resultsMMP-2 activity and p53 expression increased in proportional to the radiation dose in cell lines with wt p53, but not in the cell lines with del or mt p53. TIMP-2 expression did not increase in U87MG cells. MMP-2 activity decreased in p53 knock-downed U87MG cells but increased in the control group. Furthermore, radiation enhanced MMP-2 activity and increased tumor margin invasiveness in vivo. Tumor cells invaded by radiation overexpressed MMP-2 and p53 and revealed high gelatinolytic activity compared with those of non-radiated tumor cells.
conclusionRadiation-induced upregulation of p53 modulated MMP-2 activity, and the imbalance between MMP-2 and TIMP-2 may have an important role in glioblastoma invasion by degrading the extracellular matrix. Bioluminescent "U87-Fluc"was useful for observing tumor formation without sacrifice after implanting tumor cells in the mouse brain. These findings suggest that the radiotherapy involved field for malignant glioma needs to be reconsidered, and that future trials should investigate concurrent pharmacologic therapies that inhibit invasion associated with radiotherapy.
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