Imaging gastric cancer metastasis progression in an organotypic, three-dimensional functional model of the human peritoneum.

Abstract

Objectives: Despite the introduction of multimodal treatment regimens, the prognosis of gastric cancer peritoneal metastasis (GCPM) remains poor. To establish efficient therapies, a deeper understanding of pathophysiological mechanisms in the development of GCPM is necessary and this requires adequate functional models. Therefore, we established a three-dimensional model to study tumor adhesion, invasion and growth.

Methods: A co-culture of peritoneal mesothelial cells with fibroblasts and collagen I was cultivated to further seed human gastric cancer cell lines on the surface. Different imaging techniques (optical microscopy, immunohistochemistry, scanning (SEM) and transmission (TEM) electron microscopy) served as tools to proof the sustainability of the model.

Results: We demonstrated the feasibility of creating a robust GCPM model. We showed that the model is reproducible under various conditions (6-, 12-, and 24-wells) and pre-analytical processing is possible. The imaging was feasible and allowed the comparison of morphological changes on the GCPM model to normal human peritoneum.

Conclusions: We established a reproducible and robust organotypic model of GCPM which can be used to generate deeper knowledge on the pathophysiology of GCPM and might serve as a platform for testing different chemotherapy schemes in order to establish a personalized treatment for patients with GCPM.