Time-Dependent Micromechanical Responses of Breast Cancer Cells and Adjacent Fibroblasts to Electric Treatment |
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Authors: | Maayan?Lia?Yizraeli Email author" target="_blank">Daphne?WeihsEmail author |
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Institution: | (1) Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 32000, Israel; |
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Abstract: | Direct-current, low-intensity, electric fields were suggested as a minimally invasive treatment for various cancers. The tumor
microenvironment may affect treatment efficacy, albeit it has not generally been considered when evaluating novel anti-cancer
treatments. We evaluate the effects of electric treatment on epithelial, breast-cancer cells, co-cultured with non-cancerous
fibroblasts, a simplified model for the tumor-microenvironment. We evaluate changes in morphology, cytoskeleton, and focus
on dynamic intracellular structure and mechanics. Multiple-particle tracking was used within living cells to quantify time-dependent
structural and mechanical changes. Cancer cells suffer severe cell death and exhibit transient rounding and changes in internal
structural and mechanics. Interestingly, treating cancer cells in co-culture with fibroblasts delays and reduces their responses
to treatment. Our particle-tracking data indicates a mechanism relating the observed changes in intracellular transport to
transient changes in the microtubule network and its motors. In contrast, fibroblasts are only minimally affected by treatment,
separately or in co-culture. To conclude, intracellular mechanics reveal time-dependent responses after treatment, unavailable
by bulk measurements. This time-dependence could provide a window of opportunity for continued treatment. We demonstrate the
importance of evaluating anti-cancer treatments within their microenvironment, which can affect response magnitude and time-course. |
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