Fig. 1.

Polarized mammary structures are resistant to apoptosis induced by chemotherapeutics. When cultured on 2D monolayer, both non-malignant (A) and malignant (B) human breast cells show a similar rate of apoptosis upon treatment with distinct immunomodulators and chemical agents. However, when placed in 3D lrECM, S-1 non-malignant cells form polarized growth-arrested acini resistant to drug cytotoxic effects (C), whereas T4-2 malignant cells appear highly disorganized, proliferative and sensitive to therapeutic drugs (D). Perturbing apical–basal polarity of S-1 acini, by treatment with E-cadherin function-blocking antibody, results in a dramatic increase of sensitivity to drug agents (E). Conversely, restoring cell and tissue polarity in T4-2 structures, by treatment with β1 integrin inhibitory antibody, induces malignant cells to ‘revert’ and provides them resistance to chemotherapeutic agents (F). Polarized mammary epithelial cells are resistant to apoptosis induced by cytotoxic agents, either growth-arrested (C) or proliferating (G). In contrast, growth-arrested but reversely polarized S-1 cells grown in collagen I ECM undergo apoptosis (H, upper panel); once exposed to lrECM, these S-1 non-polar structures polarize and become resistant to apoptosis (H, lower panel).