Document Type and Release Option
Thesis (open access)
Dr. Vinoth Sittaramane
Present day cancer incidence and mortality rates indicate the need for effective cancer diagnostic tools and targeted cancer therapeutic strategies. Recent studies have focused on the biological pathways of cells and tumor microenvironments to identify putative biomarkers and potential drug targets as diagnostic and therapeutic tools. Human integrins, adhesion receptors, have become the focal points in these studies, specifically Integrin Alpha 6 (ITGA6) which has been implicated in major tumor progression roles: metastasis and angiogenesis. These characteristics make ITGA6 an excellent candidate for potential drug or diagnostic target, however, the mechanism by which ITGA6 facilitates tumor progression remains unclear. Cell culture studies have indicated ITGA6 could be cleaved extracellularly to increase metastasis but, zebrafish with organismal structures and vascular network, present a complete in vivo model to track metastasis. Our previous studies indicate that truncated ITGA6 overexpression significantly upregulates tumor metastasis compared to full-length ITGA6 overexpression. Similarly, mutated ITGA6 significantly decreases tumor metastasis. These results suggest that cleaved ITGA6 increases tumor metastasis, potentially aiding in extracellular matrix remodeling. In this study, we aim to identify the cellular role of ITGA6 by transplanting ITGA6 siRNA and DNA transfected PC3 cells into zebrafish tumor xenografts. We anticipate these experiments will help establish the cell and non-cell autonomous roles of ITGA6 during tumor development. Further, we expect to use high-resolution imaging techniques to track the migration of single cancer cells in an in vivo system to understand the dynamics of metastasis.
Williams, Ashley B., "Understanding the Mechanistic Roles of Integrin Alpha 6 in Tumor Development Using a Humanized Zebrafish (Danio rerio) Model System" (2018). Honors College Theses. 652.