3d Models Of Mesothelioma In The Study Of Mechanisms Of Cell Survival

Three-dimensional models can provide another experimental system for investigating many aspects of tumor biology, particularly of cell death and survival. These models, both in vitro and ex vivo, may be ideally suited for studying mesothelioma. Here we discuss the reports that are currently available on this subject and highlight areas in which 3D biology may provide insights into the mechanisms of cell death and survival in mesothelioma. It has long been known that single cells or monolayers are more sensitive to cell death than 3D aggregates or spheroids, which acquire resistance called "multicellular resistance." Possible survival mechanisms that have been studied using multicellular spheroids (in vitro) and tumor fragment spheroids (ex vivo) include growth factor pathways, calcium-dependent cell-cell adhesion, resistance to drug penetrance, gene expression, epigenetics, Bcl-2 anti-apoptotic family expression, and autophagy. In general, cells in a 3D setting show many differences compared to the same cells in a 2D monolayer. Many of these differences appear to contribute to cell survival. In many cases, these features can be shown to be more similar to those in the actual tumor. Thus, whereas 3D studies offer more challenges for study, they offer the opportunity for new insights not possible in 2D studies. They may thus offer an intermediate model between the monolayer and in vivo studies and hopefully lead to discoveries that can be tested in clinical trials to benefit patients.