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

## TL;DR

This study creates a 3D model of ovarian cancer metastasis using a decellularized peritoneal matrix to better understand and test new therapies.

## Contribution

The study introduces a novel 3D model using a decellularized peritoneal matrix to study ovarian cancer metastasis and therapy response.

## Key findings

- The decellularization process preserves the structural and compositional integrity of the peritoneal matrix.
- The model supports 3D growth of ovarian cancer cells and allows testing of chemotherapy and immunotherapy responses.
- Porcine peritoneal matrix shows similarities to human tissue, making it a relevant model for human physiology.

## Abstract

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.

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).

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.

Our model offers a valuable platform for investigating peritoneal carcinomatosis in HGSOC, with the potential to contribute significantly to developing novel therapeutic approaches.

Financial support was provided by the 10.13039/501100005036University of Bergen, Helse Vest RHF (F-12183-D10616, 779, 911182, 912035, and 912146), Helse Bergen HF (240222), the 10.13039/100008730Norwegian Cancer Society (6833652 and 182735), the 10.13039/501100005416Research 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 10.13039/501100002794Swedish Cancer Society (21 1888 Pj).