Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, United States
Kandice Tanner
Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, United States; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
Walter A Orellana
Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, United States; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
Clay D Reber
Bioengineering Department and Biophysics Program, University of California, Berkeley, Berkeley, United States
Douglas G Brownfield
Bioengineering Department and Biophysics Program, University of California, Berkeley, Berkeley, United States; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, United States
Bioengineering Department and Biophysics Program, University of California, Berkeley, Berkeley, United States; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, United States
Non-malignant breast epithelial cells cultured in three-dimensional laminin-rich extracellular matrix (lrECM) form well organized, growth-arrested acini, whereas malignant cells form continuously growing disorganized structures. While the mechanical properties of the microenvironment have been shown to contribute to formation of tissue-specific architecture, how transient external force influences this behavior remains largely unexplored. Here, we show that brief transient compression applied to single malignant breast cells in lrECM stimulated them to form acinar-like structures, a phenomenon we term ‘mechanical reversion.’ This is analogous to previously described phenotypic ‘reversion’ using biochemical inhibitors of oncogenic pathways. Compression stimulated nitric oxide production by malignant cells. Inhibition of nitric oxide production blocked mechanical reversion. Compression also restored coherent rotation in malignant cells, a behavior that is essential for acinus formation. We propose that external forces applied to single malignant cells restore cell-lrECM engagement and signaling lost in malignancy, allowing them to reestablish normal-like tissue architecture.
