The Functional Contribution Of Sarcoma-Associated Fibroblasts To Soft-Tissue Sarcoma Cancer Biology

Soft Tissue Sarcomas (STS) are a rare and diverse group of solid tumors derived from cells of mesenchymal lineage and can be considered a cancer of connective tissue. Our understanding of the underlying mechanisms that control STS tumor development, growth, metastasis and response to therapy is limited in comparison with other cancer types. This lack of fundamental understanding of STS biology limits progress towards the development of improved therapies. One significantly under researched area of investigation in STS is the function of recruited stromal cells, particularly sarcoma-associated fibroblasts (SAFs). This can be particularly challenging in STS subtypes that are the closest to fibroblasts in their characteristics as they express many of the same markers. This project will use a combination of in vitro 3D co-cultures of STS cells with normal mesenchymal cells, and transgenic pre-clinical models of STS that will enable the isolation of STS cells and SAFs. The project will then use RNAseq and bioinformatics analysis to identify gene expression and regulatory networks unique to SAFs before comparing their expression within clinical material and conducting further in vitro studies to understand their function in STS biology.