Figure 1. Major experimental model systems for studying cell–cell interaction.

Model systems ranges from in vitro assay of cells grown in monolayer, 3D, and spheroid/organoid cultures, to in vivo rodent carcinogenesis models, xenografts of human cancer cell lines, and patient-derived xenografts (PDXs) as well as direct analysis. The strength and weakness of each experimental model are described with red and green bars. A tradeoff exists between sample manipulation and its physiological relevance. Detailed description of each model is also summarized in Table 1.