Osteopontin and splice variant expression level in human malignant glioma: radiobiologic effects and prognosis after radiotherapy
| Autor: | Dirk Vordermark, Jörg Illert, Antje Güttler, Ariane Söling, Maria Giebler, C. Ostheimer, Jacqueline Keßler, Henri Wichmann, Christian Strauss, Matthias Kappler, Matthias Bache, Peter Cuno |
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| Rok vydání: | 2013 |
| Předmět: |
Small interfering RNA
Pathology medicine.medical_specialty 03 medical and health sciences 0302 clinical medicine stomatognathic system Glioma Cell Line Tumor medicine Humans Radiology Nuclear Medicine and imaging splice Osteopontin RNA Messenger RNA Small Interfering 030304 developmental biology 0303 health sciences Gene knockdown biology Cell growth Chemistry Brain Neoplasms Radiobiology Hematology medicine.disease Prognosis In vitro 3. Good health Oncology Apoptosis 030220 oncology & carcinogenesis Cancer research biology.protein |
| Zdroj: | Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 108(3) |
| ISSN: | 1879-0887 |
| Popis: | Background and purpose We investigated the role of the hypoxia-associated secreted glycoprotein osteopontin (OPN) in the response of malignant glioma to radiotherapy by characterizing OPN and its splice variants in vitro and in patient material. Material and methods The effect of siRNA knockdown of OPN splice variants on cellular and radiobiologic behavior was analyzed in U251MG cells using OpnS siRNA (inhibition of all OPN splice variants) and OpnAC siRNA (knockdown only of OPNa and OPNc). OPN and splice variant mRNA levels were quantified in archival material of 41 glioblastoma tumor samples. Plasma OPN was prospectively measured in 33 malignant glioma patients. Results Inhibition of OPNa and OPNc (OpnAC) reduced clonogenic survival in U251MG cells but did not affect proliferation, migration or apoptosis. Knockdown of all OPN splice variants (OpnS) resulted in an even stronger inhibition of clonogenic survival, while cell proliferation and migration were reduced and rate of apoptosis was increased. Additional irradiation had additive effects with both siRNAs. Plasma OPN increased continuously in malignant glioma patients and was associated with poor survival. Conclusions OPNb is partially able to compensate the effects of OPNa and OPNc knockdown in U251MG cells. High OPN plasma levels at the end of radiotherapy are associated with poor survival. |
| Databáze: | OpenAIRE |
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