Spatial collagen stiffening promotes collective breast cancer cell invasion by reinforcing extracellular matrix alignment.

ABSTRACT: The tumor micro-environment often contains stiff and irregular-bundled collagen fibers that are used by tumor cells to disseminate. It is still unclear how and to what extent, extracellular matrix (ECM) stiffness versus ECM bundle size and alignment dictate cancer cell invasion. Here, we have uncoupled Collagen-I bundling from stiffness by introducing inter-collagen crosslinks, combined with temperature induced aggregation of collagen bundling. Using organotypic models from mouse invasive ductal and invasive lobular breast cancers, we show that increased collagen bundling in 3D induces a generic increase in breast cancer invasion that is independent of migration mode. However, systemic collagen stiffening using advanced glycation end product (AGE) crosslinking prevents collective invasion,

SUBMITTER: Koorman T 

PROVIDER: S-EPMC9033577 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature