A 3D bioprinted liposarcoma tumor microenvironment model recapitulates stroma-driven invasion and chemoresistance

activation of TGF-β and other hallmark cancer pathways, while CAFs were activated into a pro-inflammatory, highly proliferative state. Critically, the 3D TME model conferred significant resistance to the standard chemotherapeutic agent, doxorubicin, which confirmed that this chemoresistance is mediated by a combination of physical barriers arising from cell-matrix remodeling and protective paracrine signaling from the stromal cells. In conclusion, our 3D bioprinted TME model provides a physiologically relevant and robust preclinical platform. It serves as a powerful tool for investigating the molecular mechanisms of TME-driven liposarcoma progression and chemoresistance, offering a new paradigm for the high-throughput screening of novel therapeutics that target tumor-stroma interactions.