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c-KIT-expressing Ewing tumour cells are insensitive to imatinib mesylate (STI571)
Marc Hotfilder1, Claudia Lanvers, Heribert Jürgens
1University Children's Hospital Muenster, Department of Pediatric Hematology and Oncology, University of Muenster, Albert-Schweitzer-Str. 33, 48129 Muenster, Germany.
Purpose:
In order to determine whether Ewing tumour patients may be potential candidates for imatinib mesylate therapy, we analysed the expression of the currently known imatinib mesylate-sensitive tyrosine kinases and tested sensitivity to imatinib mesylate in a panel of eight Ewing tumour cell lines in vitro.
Methods:
Expression of the different tyrosine kinases was assessed by flow cytometry and RT-PCR. Sensitivity to imatinib mesylate was analysed using a standard MTT proliferation assay.
Results:
Flow cytometric and RT-PCR analyses in a panel of eight Ewing tumour cell lines demonstrated expression of several imatinib mesylate-sensitive tyrosine kinases, including c-KIT, platelet-derived growth factor receptor, c-ABL and c-ARG. However, in the MTT proliferation assay, all eight Ewing tumour cell lines were found to be resistant to imatinib mesylate at concentrations ranging from 0.1 to 10 micro M.
Conclusions:
Despite the expression of imatinib mesylate-sensitive tyrosine kinases, Ewing tumour cells proved resistant to imatinib mesylate in vitro. This observation has implications for the selection of patients for experimental therapy with imatinib mesylate.
Insights
Ewing tumour cells express imatinib mesylate-sensitive tyrosine kinases but remain resistant to this targeted therapy in vitro. This finding impacts patient selection for imatinib mesylate treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Ewing sarcoma is a rare bone and soft tissue cancer.
- Imatinib mesylate is a tyrosine kinase inhibitor used in targeted cancer therapy.
- Identifying new therapeutic targets for Ewing sarcoma is crucial.
Purpose of the Study:
- To investigate the potential of imatinib mesylate for Ewing tumour treatment.
- To analyze the expression of imatinib mesylate-sensitive tyrosine kinases in Ewing tumour cell lines.
- To assess the in vitro sensitivity of Ewing tumour cells to imatinib mesylate.
Main Methods:
- Expression of tyrosine kinases (c-KIT, PDGFR, c-ABL, c-ARG) was analyzed using flow cytometry and RT-PCR.
- In vitro sensitivity to imatinib mesylate was evaluated through MTT proliferation assays.
Main Results:
- Ewing tumour cell lines expressed several imatinib mesylate-sensitive tyrosine kinases.
- All tested Ewing tumour cell lines demonstrated resistance to imatinib mesylate across a range of concentrations (0.1–10 µM).
Conclusions:
- Ewing tumour cells are resistant to imatinib mesylate despite expressing relevant tyrosine kinases.
- These results suggest that imatinib mesylate may not be an effective treatment for Ewing tumours.
- Further research is needed to guide patient selection for imatinib mesylate therapy.