Document Type


Degree Name



Department of Cell, Developmental, & Cancer Biology


Metastatic spread of disease accounts for the overwhelming majority of cancer-­related deaths, as current therapies are largely ineffective in treating this phase of cancer. This highlights our lack of understanding of disease progression surrounding metastatic spread of disease. Metastatic cancer cells acquire the ability to invade the surrounding environment, enter the blood stream and/or lymphatics, survive circulation, extravasate into the parenchyma of a distant organ, and proliferate as a metastatic lesion, yet the mechanisms underlying acquisition of these supporting phenotypes are not completely clear. A multitude of ways to gain metastatic potential exists, including acquired mutations and interactions with the surrounding microenvironment. Research presented in this dissertation establishes a mammary cancer model system to study metastatic disease, and investigates a novel mechanism by which cancer cells can acquire pro-­metastatic phenotypes, specifically by fusion with macrophages. Speculation around cancer cell fusion permeates the literature, but there is little evidence that spontaneous fusion actually occurs or leads to biologically relevant phenotypes. This dissertation provides experimental evidence that cell fusion is a mechanism for acquisition of metastatic phenotypes, and also presents the identification of a novel prognostic circulating biomarker that may guide treatment regimens in patients.




School of Medicine

Available for download on Friday, November 15, 2019