A 3D ovarian cancer metastasis model using a decellularized peritoneal matrix to study therapy response

High-grade serous ovarian carcinoma (HGSOC) presents a significant therapeutic challenge. Late-stage disease is frequently associated with peritoneal carcinomatosis. The peritoneal metastases exhibit a unique tumor microenvironment (TME) distinct from the primary tumors and other metastatic sites. Understanding the critical influence of the extracellular matrix (ECM) in shaping the tumor phenotype is essential for the development of effective new therapies. This study introduces a novel three-dimensional (3D) model of HGSOC peritoneal metastases using a porcine decellularized peritoneal-derived ECM scaffold, referred to as peritoneal matrix (PerMa). We show that the decellularization maintains the structural integrity and composition of ECM molecules. Comparative analysis reveals structural, compositional, and mechanical similarities between porcine and human peritoneal matrices, underscoring the porcine models translational relevance for modeling human peritoneum physiology. The PerMa supports the 3D growth of HGSOC cell lines. The model enables the assessment of sensitivity to traditional chemotherapy and novel cell-based immunotherapy through confocal imaging and quantification of cell volume. Our model offers a valuable platform for investigating peritoneal carcinomatosis in HGSOC, with the potential to contribute significantly to the development of novel therapeutic approaches.