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 model's 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.

L.B. has received honoraria for lectures from GlaxoSmithKline and Merck Sharp and has received a research grant from AstraZeneca for a researcher-initiated trial. L.B. has had leadership roles in Onkologisk Forum between 2018 and 2022 and in the Nordic Society of Gynaecological Oncology (NSGO) and NSGO-Clinical Trial Unit since 2021. She is faculty member the Gynaecological Cancers group European Society of Medical Oncology (ESMO) external expert in gynecologic oncology for the Norwegian National Expert Panel for Persons with Serious Life-Shortening Diseases and Member of the national specialist group in oncology Sykehusinnkjop HF as well as board member for KinN Therapeutics AS - a biopharmaceutical company focused on tailored preclinical oncology services for the development of novel anticancer compounds. E.M.C. is co-founder, shareholder and board member of KinN Therapeutics AS. B.D. is a consultant and speaker for MSD, AZ and GSK.

Financial support was provided by Helse Vest RHF, Helse Bergen RHF, the Norwegian Cancer Society, the Research Council of Norway (FRIPRO program (project numbers 250317, 326300) and INFRASTRUKTUR program (project number 295910), the Centre for Cancer Cell Reprogramming (CanCell), the Kolbjorn Brambani Legat for Kreftforskning, and the Swedish Cancer Society.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The regional committees for Medical and Health Research Ethics (REK West), Norway approved the biobank and the studies (Reference IDs: 2014/1907, 30477).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors