Determining the role of Ewing sarcoma derived extracellular vesicles in reprogramming of the tumor microenvironment
Mentor Name: Poul Sorensen
Ewing sarcoma (EwS) is a highly aggressive cancer and the second most common malignant bone tumor in children and young adults. The high propensity for metastasis leads to poor long-term outcome. Less toxic and more efficacious novel targeted therapeutic strategies are desperately needed. Intercellular communication within the tumor microenvironment (TME) is emerging as a crucial mechanism for cancer cells to establish immunosuppressive and cancer-permissive environments. Extracellular vesicles (EVs) offer a candidate mechanism as they are actively released by tumor cells and enriched with proteins and RNAs to communicate with other cells in the TME.
RNA-seq will be used to confirm the above results, including if EwS FLI1 controls A-to-I editing. We will perform cytokine profiling for the EwS cells +/- ADAR1 and their EVs treated fibroblasts. ViewCell RNA FISH will demonstrate the accumulation of retroelements in EwS ADAR1 +/- cells and in their EVs treated fibroblasts. For functional testing, DNA damage response, paraspeckle formation will also be tested with ViewCell RNA FISH by imaging the co-localisation of HSAT2 and other retroelements with g-H2AX-p and NEAT1/p54nrb, respectively.
