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Войти в исследования EBioMedicine · 2026
A 3D ovarian cancer metastasis model using a decellularised peritoneal matrix to study therapy response.
СтатьяНазвание и аннотация: Перевод в очереди
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Gjerde Christiane Helgestad, Kleinmanns Katrin, Langer Anika, Ruiz de Garibay Ponce Gorka, Rozmus Ezekiel, Stangeland Gina Nyhus, Leitch Calum, Elnour Rammah, Dongre Harsh Nitin, Berger Constantin, Gultekin Okan, Forcados Christopher, Stensland Maria, Nyman Tuula Anneli, Lehti Kaisa, Davidson Ben, Wälchli Sébastien, Gelebart Pascal, Costea Daniela Elena, Kotopoulis Spiros, Bjørge Line, McCormack Emmet
Аннотация
BACKGROUND: 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 tumour microenvironment (TME) distinct from the primary tumours and other metastatic sites. Understanding the critical influence of the extracellular matrix (ECM) in shaping the tumour phenotype is essential for the development of effective new therapies.
METHODS: This study introduces a three-dimensional (3D) model of HGSOC peritoneal metastases using a porcine decellularised peritoneal-derived ECM scaffold, referred to as peritoneal matrix (PerMa).
FINDINGS: We show that the decellularisation 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 modelling 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.
INTERPRETATION: Our model offers a valuable platform for investigating peritoneal carcinomatosis in HGSOC, with the potential to contribute significantly to developing novel therapeutic approaches.
FUNDING: Financial support was provided by the University of Bergen, Helse Vest RHF (F-12183-D10616, 779, 911182, 912035, and 912146), Helse Bergen HF (240222), the Norwegian Cancer Society (6833652 and 182735), the Research Council of Norway grants (250317, 326300, 223250, 262652, and 295910), the Novo Nordisk Foundation (NNF21OC0070381), the Kolbjørn Brambani Legat for Kreftforskning, the National Institute of Health (R01CA199646) and the Swedish Cancer Society (21 1888 Pj).
METHODS: This study introduces a three-dimensional (3D) model of HGSOC peritoneal metastases using a porcine decellularised peritoneal-derived ECM scaffold, referred to as peritoneal matrix (PerMa).
FINDINGS: We show that the decellularisation 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 modelling 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.
INTERPRETATION: Our model offers a valuable platform for investigating peritoneal carcinomatosis in HGSOC, with the potential to contribute significantly to developing novel therapeutic approaches.
FUNDING: Financial support was provided by the University of Bergen, Helse Vest RHF (F-12183-D10616, 779, 911182, 912035, and 912146), Helse Bergen HF (240222), the Norwegian Cancer Society (6833652 and 182735), the Research Council of Norway grants (250317, 326300, 223250, 262652, and 295910), the Novo Nordisk Foundation (NNF21OC0070381), the Kolbjørn Brambani Legat for Kreftforskning, the National Institute of Health (R01CA199646) and the Swedish Cancer Society (21 1888 Pj).