Role of Type III TGF-β Receptor Shedding in Regulating Tumorigenesis
Date
2019
Authors
Advisors
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Abstract
The type III TGF-β receptor (TβRIII) is a TGF-β co-receptor that presents ligand to the type II TGF-β receptor to initiate signaling. TβRIII also undergoes ectodomain shedding to release a soluble form (sTβRIII) that can bind ligand, sequestering it away from cell surface receptors. We have previously identified a TβRIII extracellular mutant that has enhanced ectodomain shedding (“super shedding (SS)” – TβRIII-SS). Here we utilize TβRIII-SS to study the balance of cell surface and soluble TβRIII in the context of lung cancer. We demonstrate that expressing TβRIII-SS in lung cancer cell models induces epithelial-mesenchymal transition (EMT) and that these TβRIII-SS (EMT) cells are less migratory, invasive and adhesive and more resistance to gemcitabine. Moreover, TβRIII-SS (EMT) cells exhibit decreased tumorigenicity but increased tumor growth in vitro and in vivo. These studies suggest that the balance of cell surface and soluble TβRIII may regulate a dichotomous role for TβRIII during cancer progression.
We have also demonstrated that cathepsin G and neutrophil elastase, proteases stored in the azurophil granules of neutrophils, can induce cleavage of cell surface TβRIII though no functional sTβRIII was detected. Similarly, activated neutrophils could induce TβRIII shedding on cancer cells. Interestingly, neutrophils generate sTβRIII that is resistant to shedding. These studies suggest that neutrophils may modulate the balance of cell surface and soluble TβRIII in the tumor microenvironment.
Type
Department
Description
Provenance
Citation
Permalink
Citation
Huang, Jennifer J. (2019). Role of Type III TGF-β Receptor Shedding in Regulating Tumorigenesis. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/18645.
Collections
Except where otherwise noted, student scholarship that was shared on DukeSpace after 2009 is made available to the public under a Creative Commons Attribution / Non-commercial / No derivatives (CC-BY-NC-ND) license. All rights in student work shared on DukeSpace before 2009 remain with the author and/or their designee, whose permission may be required for reuse.