Elucidating Metastatic Behavior Through Nanopatterned Membranes

摘要

The DA award entitled 'Elucidating Metastatic Behavior Through Nanopatterned Membranes' proposed to study the behavior of live human breast cancer cells (out of a library of over 60 cell lines) on artificial surfaces that mimic the microenvironment encountered in normal tissue. Natively membrane- bound ephrin-A1, which activates the cancer-associated receptor tyrosine kinase (RTK) EphA2 (1,2), is tethered to a two-dimensionally fluid supported membrane. Live human breast cancer cells expressing EphA2 are then engaged with these surfaces, and subsequent changes in receptor spatial organization, signaling, and cell behavior are quantified. Finally, the response of cells to various drugs can be measured to find effective treatments that change diseased-cell behavior. This approach may provide for cost effective, rapid, single-cell diagnostic assays that can better match therapeutics to patients. The use of supported membranes to study cancer behavior at the single cell level is an entirely new avenue for breast cancer diagnostics and if successful will provide for an assay that complements existing biomarker based diagnostics.