Oncolytic Vesicular Stomatitis Virus Inhibits Cancer Cell Invasion Processes

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Dakota W. Goad (Creator)
Institution
Appalachian State University (ASU )
Web Site: http://www.library.appstate.edu/
Advisor
Maryam Ahmed

Abstract: Vesicular stomatitis virus (VSV) is being investigated as an oncolytic agent due to its capacity to kill cancer cells while exhibiting low virulence in vivo. A trigger for cancer metastasis is the formation of structures known as invadopodia, which function in extracellular matrix (ECM) degradation. I hypothesized that VSV alters invadopodia structures and inhibits their proteolytic function due to the ability of VSV to inhibit host gene expression. My results showed that, following infection with VSV, Src-transformed fibroblasts formed lowered numbers of invadopodia, but yielded increased numbers of ring shaped invadopodia superstructures called rosettes. Overall, there was a decreased ability of cells to degrade ECM and express the invadopodia marker protein, Tks5, both of which correlated with the suppression of invadopodia. These results suggest that alteration in invadopodia by VSV is associated with its ability to decrease proteolytic degradation of ECM. Interestingly, we found an increase in cortactin expression which may be related to increased rosette structures at later times post-infection. Our results suggest that manipulation of cytoskeletal elements by VSV may be a mechanism by which VSV potentiates the infection process, but may lead to the downstream effect of altering proteolytic activity of cancer cells, inhibiting the invasion process.

Additional Information

Publication
Thesis
Goad, D. (2017). "Oncolytic Vesicular Stomatitis Virus Inhibits Cancer Cell Invasion Processes." Unpublished Master’s Thesis. Appalachian State University, Boone, NC.
Language: English
Date: 2017
Keywords
Oncolytic Virotherapy, Vesicular Stomatitis Virus, Metastasis, Invadopodia, Actin Cytoskeleton

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