Using Novel Genetically Engineered Mouse Models of Soft Tissue Sarcoma to Interrogate the Contribution of Cell of Origin and Tissue Injury to Sarcoma Development
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2015
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Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors comprised of >70 subtypes. An important question is how the cell of origin and the pathways to tumor development shape the broad array of STS subtypes. By forcing identical tumor-promoting mutations to different cell types in Genetically Engineered Mouse Models (GEMMs) of STS, I have a unique model system to investigate this question. In the process of performing these experiments I observed that genetic mutations are necessary, but not sufficient for rapid sarcoma formation. However, tissue injury dramatically accelerates sarcoma formation in our GEMM of STS. For my thesis, I have worked to understand how cell of origin affects sarcoma subtype and how the microenvironment in our models promotes transformation. I have observed that cell of origin plays an important, but not the only, role in defining STS subtype. Additionally, I have concluded that the microenvironment, and specifically the HGF/c-MET signaling pathway play a crucial role in promoting sarcoma development after acute tissue injury.
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Stephens, Leonor Ano (2015). Using Novel Genetically Engineered Mouse Models of Soft Tissue Sarcoma to Interrogate the Contribution of Cell of Origin and Tissue Injury to Sarcoma Development. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/9877.
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