Dynamically stiffened matrix promotes malignant transformation of mammary epithelial cells via collective mechanical signaling.

ABSTRACT: Breast cancer development is associated with increasing tissue stiffness over years. To more accurately mimic the onset of gradual matrix stiffening, which is not feasible with conventional static hydrogels, mammary epithelial cells (MECs) were cultured on methacrylated hyaluronic acid hydrogels whose stiffness can be dynamically modulated from "normal" (<150 Pascals) to "malignant" (>3,000 Pascals) via two-stage polymerization. MECs form and remain as spheroids, but begin to lose epithelial characteristics and gain mesenchymal morphology upon matrix stiffening. However, both the degree of matrix stiffening and culture time before stiffening play important roles in regulating this conversion as, in both cases, a subset of mammary spheroids remained insensitive to local matrix stiffness. Th

SUBMITTER: Ondeck MG 

PROVIDER: S-EPMC6397509 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature