Document Type and Release Option
Thesis (restricted to Georgia Southern)
Dr. Vinoth Sittaramane
Despite overall declines in cancer mortality rates over the last two decades, cancer remains the second leading cause of death in the United States. Metastasis, the migration of a tumor cell from its primary growth site to a distant site where it grows and develops into a secondary tumor, is responsible for 90 percent of all cancer patient mortalities. Despite their implications, the mechanisms by which tumor cells invade have yet to be fully elucidated. Therefore, the employment of methods and model systems that allow for further insight into the mechanisms and key molecular players implicated in metastasis, like ITGA6, are of great interest. Zebrafish has emerged as an important model system due to its ease of genetic manipulation, high fecundity, high-throughput capability. Here, they are utilized to track metastasis of MDA-MB-231 and PC3 cells over long term time-lapses, which allow for a deeper appreciation of malignant cell behavior. Due to extracellular matrix (ECM) degradation or remodeling being required for cell metastasis, attempts to visualize changes in the 3D architecture of the ECM proteins laminin and cadherin in result of malignant phenotypes are also made by utilizing tissue cross-sections of zebrafish exhibiting head MDA-MB-231 metastases. Lastly, ECM remodeling often occurs through matrix metalloproteinases (MMPs). GM6001, a broad range MMP inhibitor, is used to treat zebrafish with PC3 tumor xenografts, alongside those control, in aims of visualizing differences in metastasis over long term time-lapses.
Loveless, Reid D., "Understanding the Tumor Microenvironment Using Humanized Zebrafish Tumor Xenograft Model" (2018). University Honors Program Theses. 395.