A Unique Opportunity To Test Whether Cell Fusion Is a Mechanism of Breast Cancer Metastasis
Technical Report,01 Jul 2011,31 May 2016
University of Minnesota-Twin Cities Minneapolis United States
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The goal of this proposal was to determine whether cell fusion between tumor cells and hematopoietic cells is the precipitating event for breast cancer metastasis and whether viral fusion proteins enable or catalyze this event. Our results suggest therapeutic strategies to disrupt or inhibit cell fusion could reduce tumor heterogeneity and limit the formation of metastases. In support of this statement we demonstrated the following in the course of the funded award. First, we found mesenchymal stem cells are a potent fusion partner for breast cancer cells of all phenotypes. Fusion occurred spontaneously at rates of up to 1 in 250cells. Rates were increased with decreased availability of oxygen. This finding is especially relevant given the hypoxic nature of the tumor microenvironment. Fusion products were able to migrate faster and invade collagen gels more rapidly and at greater distances than unfused counterparts. In addition, the transcriptome of fusion products was highly diverse, capable of upregulating critical oncogenes and down regulating tumor suppressors. Further, we found apoptotic cells can promote cell fusion and we are now extending this line of study to identify molecular targets on cancer cells that are responsive to apoptotic cell engagement, especially members the receptor family for lipid engagement. Such targets could prove quite useful for the development of a new class of pharmaceutical agent capable of inhibiting or limiting cell-cell fusion.
- Medicine and Medical Research