A three-dimensional in-vitro model for the study of peritoneal tumour metastasis.

Abstract

Peritoneal metastasis is a frequent complication of gastrointestinal malignancy. We have developed a three-dimensional model of the human peritoneum that simulates the metastatic process in vitro. Peritoneal fibroblasts were incorporated into collagen lattices, allowed to contract, then overlaid with mesothelial cells. Scanning and transmission electron microscopy showed the model to have similar physical properties to human peritoneum. Mesothelial expression of the beta1 integrin family, the basement membrane proteins fibronectin, laminin, collagen types III and IV, and the cell adhesion molecules ICAM-1, VCAM-1 and PECAM were assessed and showed similar results to in vivo tissue. Gastrointestinal tumour cells seeded onto the model exhibited mesothelial adhesion, cell spreading and vesicle formation, and invasion of the mesothelial monolayer on scanning electron microscopy. Two distinct patterns of tumour cell growth were observed using light microscopy: a superficial spreading layer, and discrete invasive deposits. Invasion was accompanied by disruption of the mesothelial monolayer, degradation and re-orientation of the matrix, and rudimentary tumour cell differentiation. We believe the use of this in vitro peritoneal model will facilitate the study of the molecular mechanisms involved in the metastatic process.