Physiological elasticity and topography modulate in vitro prostate cancer cell behavior

Tissue elasticity and microenvironment are a hallmark of cancer, particularly in prostate cancer. Here, we investigate, how physiologically relevant mechanical properties affect prostate cancer cells using 2D-poly(dimethylsiloxane) (PDMS) and topographic 2.5D-poly(ethylene glycol) diacrylate-glycidyl methacrylate hydrogel surfaces. Substrates reproducing the stiffness of tumor cell niches, altered cell morphology, metabolic activity, migration, cytokine expression, and therapeutic response. Elasticity-dependent effects included up to a 1.5-fold increase in LDH activity with concurrent cell proliferation, reduced migration rates with increased paxillin expression, and enhanced chemokine-mediated invasion. Adaptation to physiological elasticities was also associated with up to 90 % reduction in responsiveness to docetaxel and enzalutamide. Importantly, elasticity-adapted substrates supported primary prostate cancer cell growth while preserving characteristic expression profiles. These findings demonstrated that mechanical microenvironmental cues substantially shape prostate cancer cell phenotypes and highlight their importance for developing more physiologically relevant and translationally informative in vitro models.