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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2014

Authors: Walter, I; Wolfesberger, B; Miller, I; Mair, G; Burger, S; Gallè, B; Steinborn, R

Title: Human osteosarcoma cells respond to sorafenib chemotherapy by downregulation of the tumor progression factors S100A4, CXCR4 and the oncogene FOS.

Source: Oncol Rep. 2014; 31(3):1147-1156

Authors Vetmeduni Vienna:

Burger Stefanie
Mair Georg
Miller Ingrid
Steinborn Ralf
Walter Ingrid
Wolfesberger Birgitt

Vetmed Research Units
University Clinic for Small Animals, Clinical Unit of Internal Medicine Small Animals
Institute for Medical Biochemistry
Institute of Morphology
Laboratory of Tropical Veterinary Medicine

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.

Keywords Pubmed: Antineoplastic Agents/pharmacology*
Bone Neoplasms
Cell Line, Tumor
Drug Screening Assays, Antitumor
Gene Expression Regulation, Neoplastic/drug effects
Niacinamide/analogs & derivatives*
Oligonucleotide Array Sequence Analysis
Oncogene Proteins v-fos/genetics
Oncogene Proteins v-fos/metabolism*
Phenylurea Compounds/pharmacology*
Receptors, CXCR4/genetics
Receptors, CXCR4/metabolism*
S100 Proteins/genetics
S100 Proteins/metabolism*
Transcriptome/drug effects

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