A Unique Opportunity to Test Whether Cell Fusion is a Mechanism of Breast Cancer Metastasis
Annual rept. 1 Jul 2011-30 Jun 2012
WISCONSIN UNIV MADISON
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The goal of this proposal is 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. If successful, this discovery would dramatically change our approach to breast cancer therapy in the following specific ways. To date we have completed a significant portion of the tasks delineated in Aim 1. First we have optimized protocols for the separation of myeloid and monocyte populations from human mononuclear cell populations. Also we have optimized electroporation conditions for T47D and human mesenchymal stem cell populations. As a result we have been able to conduct our first co-culture experiments to determine whether breast cancer cells fuse spontaneously with hematopoietic cell types. Preliminary results suggest these populations do fuse spontaneously and that fusion products formed in this way can survive several days and are capable of proliferation. In the upcoming months, combinatorial co-cultures with different blood cell subpopulations myeloid, lymphoid, and monocyte and healthy or diseased mammary lines will be performed to determine the frequency of fusion between these subpopulations. The effect of hypoxia and hypoglycemia on the frequency of fusion will also be determined. Identified fusion products will then be purified via flow cytometry and assessed for the capacity to migrate and proliferate.
- Medicine and Medical Research