Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Walter, I; Wolfesberger, B; Miller, I; Mair, G; Burger, S; Gallè, B; Steinborn, R.
Human osteosarcoma cells respond to sorafenib chemotherapy by downregulation of the tumor progression factors S100A4, CXCR4 and the oncogene FOS.
Oncol Rep. 2014; 31(3):1147-1156
Doi: 10.3892/or.2013.2954
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- Co-authors Med Uni Graz
- Gallé Birgit
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- Abstract:
- Osteosarcoma is a rare but aggressive bone neoplasm in humans, which is commonly treated with surgery, classical chemotherapy and radiation. Sorafenib, an inhibitor of a number of kinases targeting the Raf/MEK/ERK pathway, is a promising new chemotherapeutic agent in human medicine that has been approved since 2006 for the therapy of renal cell carcinoma and since 2007 for the treatment of hepatocellular carcinoma. Here, we studied the antimetastatic potential of 4 µM of this multikinase inhibitor in a human osteosarcoma cell line. DNA microarray-based gene expression profiling detected 297 and 232 genes upregulated or downregulated at a threshold of >2-fold expression alteration (P<0.05) in the sorafenib-treated cells. Three genes (CXCR4, FOS and S100A4) that are involved in tumor progression were chosen for validation by quantitative PCR (qPCR) and protein expression analysis. The decrease in RNA expression detected by microarray profiling was confirmed by qPCR for all three genes (P<0.01). On the protein level, sorafenib-induced reduction of S100A4 was verified both by western blotting and immunohistochemistry. For CXCR4 and c-Fos, a reduced protein expression was shown by immunohistochemistry, for c-Fos also by immunoblotting. We conclude that sorafenib could serve as a potent chemotherapeutical agent by which to inhibit the metastatic progression of osteosarcomas.
- Find related publications in this database (using NLM MeSH Indexing)
- Antineoplastic Agents - pharmacology
- Bone Neoplasms -
- Cell Line, Tumor -
- Down-Regulation -
- Drug Screening Assays, Antitumor -
- Gene Expression Regulation, Neoplastic - drug effects
- Humans -
- Niacinamide - analogs & derivatives
- Niacinamide - pharmacology
- Oligonucleotide Array Sequence Analysis -
- Oncogene Proteins v-fos - genetics
- Oncogene Proteins v-fos - metabolism
- Osteosarcoma -
- Phenylurea Compounds - pharmacology
- Receptors, CXCR4 - genetics
- Receptors, CXCR4 - metabolism
- S100 Calcium-Binding Protein A4 -
- S100 Proteins - genetics
- S100 Proteins - metabolism
- Sorafenib -
- Transcriptome - drug effects
- Find related publications in this database (Keywords)
- S100A4
- c-Fos
- CXCR4
- osteosarcoma cells
- sorafenib
- human