Cell-Cell Fusion in Cancer: Key In Silico Tumor Evolutionary Behaviors

PaulameenaShultes

Case Western Reserve University

"Cell-Cell Fusion in Cancer: Key In Silico Tumor Evolutionary Behaviors"

Cell-cell fusion is a known phenomenon throughout the human body. It characterizes a wide range of physiological and pathological processes, ranging from placentation and embryogenesis to cancer stem cell (CSC) formation. There is increasing evidence that cell-cell fusion can play key roles in the development and progression of cancer, particularly by increasing intratumor heterogeneity and potentiating somatic evolution. There are many unanswered questions surrounding the characteristics that define cancer cell-cell fusion events, their frequency in in vivo tumor conditions, and whether or not cell-cell fusion is a universal phenomenon across cancer. Using a combination of in vitro and in silico approaches, we can begin to answer some of these questions. We have developed a preliminary cellular automata model using HAL to evaluate the effect of variable cell-cell fusion rates and behaviors under a range of tumor microenvironmental conditions. By comparing our spatial model to a suite of ordinary differential equations, we can begin to estimate the effects of cell-cell fusion on the genomic heterogeneity and malignancy potential of cancers in vivo. I demonstrate the importance of improving fusion rate estimates using the simplest iteration of an in silico cellular automata model (coined SimpleFusion). The preliminary SimpleFusion model results illustrate how much the impact of cell fusion, as measured by the percentage of cells that have had a fusion event in their lineage, changes between orders of magnitude of fusion rates. Corresponding ODE models demonstrate similar results despite the lack of encoded spatial information. By studying these two types of models (ABM, ODEs) in combination, we can begin to understand what parameters most directly define the cell-cell fusion population dynamics in our in vitro fusion experiments and, in turn, in vivo conditions as well.
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