Wild-Type And Matrix Protein Mutant Strains Of Vesicular Stomatitis Virus Differentially Modulate Podosome Development In M1 And M2 Macrophage Populations

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Dalton Patrick Sizemore (Creator)
Institution
Appalachian State University (ASU )
Web Site: https://library.appstate.edu/
Advisor
Darren Seals

Abstract: Macrophages of the tumor microenvironment form cytoskeletal adhesion structures called podosomes that facilitate invasive behavior of cancer cells through degradation of extracellular matrix proteins. This study investigates whether macrophage podosomes are a therapeutic target of oncolytic strains of vesicular stomatitis virus (VSV). This was accomplished by testing recombinant wild-type (rwt) and matrix (M) protein mutant (rM51R-M) strains of VSV on podosomes in model THP-1 cells and in macrophages derived from primary blood mononuclear cells (PBMCs). Macrophages exhibit a range of phenotypes between two polarization extremes: classically-activated, cancer-fighting M1s and alternatively-activated, cancer-promoting M2s. Here we show that while M2s form more podosomes than M1s, they are initially less effective at degradation. Both VSV strains were able to reduce podosome multiplicity in M2s and matrix-degrading podosome activity in M1s. To address the mechanism behind these results, podosome- and polarization-associated transcript levels were monitored. Evidence is also provided for how VSV infection may induce a possible hybrid macrophage phenotype with both M1 and M2 characteristics. These results collectively provide further evidence that oncolytic VSV strains not only effectively kill tumor cells but have the potential to act as potent immunogenic agents through the modulation of macrophage populations in the tumor microenvironment.

Additional Information

Publication
Thesis
Sizemore, D. (2021). Wild-Type And Matrix Protein Mutant Strains Of Vesicular Stomatitis Virus Differentially Modulate Podosome Development In M1 And M2 Macrophage Populations. Unpublished Master’s Thesis. Appalachian State University, Boone, NC.
Language: English
Date: 2021
Keywords
Macrophage, Vesicular Stomatitis Virus, Podosome, Tumor Microenvironment

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