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

Peritoneal metastasis is a frequent complication of gastrointestinal malign ancy. We have developed a three-dimensional model of the human peritoneum t hat simulates the metastatic process in vitro. Peritoneal fibroblasts were incorporated into collagen lattices, allowed to contract, then overlaid wit h mesothelial cells. Scanning and transmission electron microscopy showed t he model to have similar physical properties to human peritoneum. Mesotheli al expression of the beta 1 integrin family, the basement membrane proteins fibronectin, laminin, collagen types III and IV, and the cell adhesion mol ecules ICAM-1, VCAM-1 and PECAM were assessed and showed similar results to in vivo tissue. Gastrointestinal tumour cells seeded onto the model exhibi ted mesothelial adhesion, cell spreading and vesicle formation, and invasio n of the mesothelial monolayer on scanning electron microscopy. Two distinc t patterns of tumour cell growth were observed using light microscopy: a su perficial spreading layer, and discrete invasive deposits. Invasion was acc ompanied by disruption of the mesothelial monolayer, degradation and re-ori entation of the matrix, and rudimentary tumour cell differentiation. We bel ieve the use of this in vitro peritoneal model will facilitate the study of the molecular mechanisms involved in the metastatic process.