Professor Adrienne Flanagan, Royal National Orthopaedic Hospital, Middlesex (£28,800)
Cancer stem cells in Osteosarcoma: potential for development of new prognostic markers and treatment.
Purpose: To conduct a pilot study of osteosarcoma (OS) and Ewing sarcoma (ES) in persons aged 0-24 years as the forerunner of a multi-centre international case-control study.
Recent findings support the theory that tumours include and may be initiated by a distinct cancer stem cell (CSC) population, and that identifying and eliminating this population is key to cancer treatment and cure. The identification of the CSC population may have particular relevance in osteosarcomas where survival has reached a plateau, and more innovative approaches to treatment are required.
This project aims to identify and characterise the CSC population in osteosarcoma through 3 steps:
- Performing immunohistochemistry on tissue sections and tissue microarrays comprising 200 paraffin-embedded osteosarcomas in order to identify the proportion of the cells expressing known stem cell markers and the distribution of this population within the tumour. Tumours previously treated with chemotherapy will also be included to identify whether the surviving cells express stem cell markers.
- Selecting the above cells from fresh tumour samples by FACS sorting and injecting these into immuno-suppressed (NOD-SCID) mice using a range of dilutions, in order to induce tumour formation. Histological analysis of mouse tumours will indicate whether the CSCs recapitulate the human tumours of origin.
- Optimisation of the in vitro culture conditions for the CSCs and determination of their differentiation potential and upregulated signal transduction networks
The results of this project will indicate the proportion of CSCs present in osteosarcomas, whether these cells are resistant to chemotherapy and their tumorigenic nature as determined by mouse xenografts. The results are likely to lead to new prognostic and treatment alternatives for ostesarcomas.
