Related Experiment Videos
TPA-mediated regulation of osteopontin in human malignant glioma cells
M A Tucker1, P L Chang, C W Prince
1Department of Nutrition Sciences, University of Alabama at Birmingham 35294, USA.
Abstract:
Malignant gliomas are the most common primary intracranial neoplasms in adults and are largely refractory to post-surgical therapy despite intensive therapeutic efforts. Using a number of different brain tumor-derived cell lines we have demonstrated that the mRNA for osteopontin (OPN), which is substantially over-expressed by some tumors in comparison with normal tissues, is preferentially expressed in high grade and metastatic brain tumors compared to low grade brain tumors. One glioma-derived cell line, U105MG, which does not express significant amounts of OPN mRNA, could be induced dose-dependently by the tumor-promoting and PKC-activating phorbol ester, TPA, to over-express OPN mRNA in a PKC-dependent manner. Unexpectedly, treatment of U105MG cells with Ca2+ ionophore (A23187) completely inhibited TPA-mediated induction of OPN while treatment with the intracellular Ca2+ antagonist TMB-8 had no significant effect. Elucidation of regulatory mechanisms for OPN induction in glioma cells should facilitate rational design of novel therapeutics for human malignant gliomas.
Insights
Osteopontin (OPN) is over-expressed in high-grade malignant gliomas. Protein kinase C (PKC) activation can induce OPN expression, but calcium ions inhibit this induction, offering potential therapeutic targets.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Malignant gliomas are aggressive brain tumors with limited treatment options.
- Osteopontin (OPN) is a protein implicated in tumor progression and metastasis.
- OPN expression varies significantly between glioma grades.
Purpose of the Study:
- To investigate the expression patterns of osteopontin (OPN) mRNA in different grades of malignant gliomas.
- To explore the regulatory mechanisms of OPN induction in glioma cells, focusing on protein kinase C (PKC) and calcium signaling.
Main Methods:
- Analysis of OPN mRNA expression in various human glioma cell lines.
- Induction of OPN expression using phorbol ester (TPA) and protein kinase C (PKC) activators.
- Investigation of the role of calcium ions (Ca2+) using calcium ionophore (A23187) and intracellular calcium antagonist (TMB-8).
Main Results:
- Osteopontin (OPN) mRNA is preferentially expressed in high-grade and metastatic brain tumors compared to low-grade gliomas.
- Tumor-promoting phorbol ester (TPA) induced OPN mRNA expression in a dose-dependent and PKC-dependent manner in U105MG glioma cells.
- Calcium ionophore (A23187) unexpectedly inhibited TPA-mediated OPN induction, while TMB-8 had no significant effect.
Conclusions:
- Osteopontin (OPN) is a potential biomarker for high-grade malignant gliomas.
- PKC signaling is involved in regulating OPN expression in glioma cells.
- Calcium signaling pathways play a complex, inhibitory role in OPN induction, suggesting novel therapeutic strategies for malignant gliomas.