Enhancing therapeutic efficacy through degradation of endogenous extracellular matrix in primary breast tumor spheroids

• DOI: 10.1111/febs.70069
• Publication Date: 2025-03-18T05:59:32Z
• Authors: Alessandra Lo Cicero; Simona Campora; Gabriele Lo Buglio; Paolo Cinà; Margot Lo Pinto; Simone Dario Scil...; Giulio Ghersi
• Keywords: Spheroid

Solid tumors have a complex extracellular matrix (ECM) that significantly affects tumor behavior and response to therapy. Understanding the ECM's role is crucial for advancing cancer research treatment. This study established an in vitro model using primary cells isolated from rat breast generate three‐dimensional spheroids. Monolayer spheroid cultures exhibited different protein expression patterns, with spheroids presenting increased level of ECM‐related proteins more environment. Furthermore, produce endogenous collagen type I matrix, which main component tumoral ECM. arranged predominantly around 3D structure, mimicking conditions solid tumors. Treatments recombinant collagenases class II (acting on linear region) 3D‐helix completely degrade within structure. Collagenase pretreatment enhances accessibility anticancer drug doxorubicin penetrate core sensitize them doxorubicin‐induced cytotoxicity. Our findings highlight importance overcoming resistance by targeting ECM proposing novel strategy improving therapeutic outcomes By employing model, ECM, we can offer relevant insights into biology treatment responses.