Stiffness and viscoelasticity of adipose tissue decellularized extracellular matrix hydrogels influence proliferation, growth pattern, migration and invasion of breast cancer cells

Breast cancer progression is strongly influenced by the physicochemical properties of the surrounding extracellular matrix (ECM). To model the breast ECM, adipose tissue decellularized extracellular matrix (dECM)-derived hydrogels were generated, which preserve a broad spectrum of ECM associated proteins and exhibit stiffness and viscoelastic properties within the physiological range of breast tissue. Proteomic analyses confirmed the biochemical complexity of these materials, while rheological measurements established their mechanically relevant characteristics. Within these 3D dECM hydrogels, the poorly metastatic MCF 7 and highly invasive MDA MB 231 cell lines displayed their expected lineage specific behaviors. Moreover, these cells exhibited significantly distinct proliferation, invasion, and growth patterns in hydrogels with different stiffness and viscoelasticity, highlighting the importance of biophysical cues in modulating cell phenotype. These findings illustrate that user-friendly adipose tissue dECM hydrogels provide a biologically meaningful platform for investigating how microenvironmental mechanics influence cell behavior.