Stiffness and Viscoelasticity of Adipose Tissue Decellularized Extracellular Matrix Hydrogels Influence Proliferation, Growth Pattern, Migration and Invasion of Breast Cancer Cells

Abstract Breast cancer remains the leading cause of cancer-related mortality among women. Cellular behavior is influenced by the physicochemical factors of the extracellular matrix (ECM) surrounding them. In order to model the breast ECM, adipose tissue decellularized extracellular matrix (dECM)-derived hydrogels are generated, which retain the full biochemical complexity of the source tissue, while also exhibiting stiffness and viscoelastic properties comparable to those of breast tissue. By recapitulating the characteristics of their native environment, validated through proteomic analysis and rheology, the poorly metastatic MCF-7 and the highly invasive MDA-MB-231 breast cancer cell lines exhibit their archetypal behaviors within the 3D hydrogels. Moreover, these cells display significantly distinct proliferation, invasion, and growth patterns in hydrogels with different stiffness and viscoelasticity, highlighting the importance of biophysical parameters in modulating cell phenotype. These results illustrate that user-friendly 3D biomaterial models based on adipose tissue dECM can effectively replicate crucial aspects of in vivo cellular behavior. Table of Contents This study presents 3D hydrogels derived from porcine adipose tissue dECM that mimic biophysical and biochemical properties of breast tissue. Two breast cancer cell lines mimicking luminal and triple-negative subtypes, exhibited distinct proliferation, migration, and invasion behaviors depending on hydrogel stiffness and viscoelasticity. The results highlight how biophysical cues shape cell phenotype in a user-friendly 3D model. Competing Interest Statement The authors have declared no competing interest.