Date of Graduation

Summer 8-13-2013

Document Type

Thesis

Degree Name

Master of Science (MS)

Department/Program

Biology

First Advisor

Juliet Spencer

Second Advisor

Christina Tzagarakis-Foster

Third Advisor

John Sullivan

Abstract

Human cytomegalovirus (HCMV) is a highly species-specific, common human pathogen. While a large majority of people are infected with HCMV worldwide, infection is typically asymptomatic in immune competent individuals. To enhance virus persistence and avoid immune detection by the host, HCMV exploits the strategy of encoding homologs of cellular cytokines. One factor produced by HCMV-infected cells is the viral cytokine cmvIL-10, which acts through the cellular IL-10 receptor to induce downstream cell signaling. In instances where HCMV-infected cells infiltrate the tumor microenvironment, the presence of cmvIL-10 in may initiate events that promote a more invasive tumor phenotype. Cancer cells that express fewer adhesion molecules, which allow cells to break off from the primary tumor, are more likely to metastasize. In addition, matrix metalloproteinases (MMPs) degrade the extracellular matrix, which promotes cancer cell dissemination by permitting tumor cells access to the vascular and lymphatic systems. We found that MCF-7 human breast cancer cells express the cellular IL-10 receptor and that treatment with cmvIL-10 results in changes in gene expression and cellular activity related to cancer progression. We demonstrate that cmvIL-10 alters expression of cell adhesion molecules and increases MMP gene expression. Breast cancer cells also exhibit more robust migration in the presence of cmvIL-10. CmvIL-10 may cooperate with other factors secreted by HCMV infected cells, and the secretome of HCMV infected fibroblasts are characterized. The results indicate that breast cancer cells exposed to cmvIL-10 undergo changes that could lead to the formation of more invasive tumors. This suggests that HCMV-positive cancer patients may have the potential to develop more metastases and could benefit from the inclusion of anti-viral therapeutics in their treatment regimen.

Comments

With much gratitude, Robin Kristine Bishop

MissRobinBishop@gmail.com

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