3D tumour models: novel in vitro approaches to cancer studies

Abstract

3D in vitro models have been used in cancer research as a compromise between 2-dimensional cultures of isolated cancer cells and the manufactured complexity of xenografts of human cancers in immunocompromised animal hosts. 3D models can be tailored to be biomimetic and accurately recapitulate the native in vivo scenario in which they are found. These 3D in vitro models provide an important alternative to both complex in vivo whole organism approaches, and 2D culture with its spatial limitations. Approaches to create more biomimetic 3D models of cancer include, but are not limited to, (i) providing the appropriate matrix components in a 3D configuration found in vivo, (ii) coculturing cancer cells, endothelial cells and other associated cells in a spatially relevant manner, (iii) monitoring and controlling hypoxia-to mimic levels found in native tumours and (iv) monitoring the release of angiogenic factors by cancer cells in response to hypoxia. This article aims to overview current 3D in vitro models of cancer and review strategies employed by researchers to tackle these aspects with special reference to recent promising developments, as well as the current limitations of 2D cultures and in vivo models. 3D in vitro models provide an important alternative to both complex in vivo whole organism approaches, and 2D culture with its spatial limitations. Here we review current strategies in the field of modelling cancer, with special reference to advances in complex 3D in vitro models.

Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro–in vivo gap

“…Another approach is the use of natural or synthetic hydrogels as a scaffold in which cells can be seeded 211 . Hydrogel-based scaffolds are however likely to be not very useful for NP studies as thick scaffolds will limit the diffusion of NP towards the cells, which will drastically alter the outcome of any uptake or toxicity studies.…”

Cellular heterogeneity mediates inherent sensitivity–specificity tradeoff in cancer targeting by synthetic circuits

“…However, further elucidation is required to account for cell-cell communication, bystander effect, or gene/drug penetration when addressing the targeting of spatially constrained cells. For example, 3D-tumor models closer to real-life tumors are important to study the actual capability of synthetic circuits in cancer therapy (33)(34)(35). Toward a predictive sensitivity/specificity model, the intrinsic response function of the circuit should be combined with spatial organization and cell-type-specific features such as kinetics of growth, overall metabolism, and dose-response (36).…”

β1 integrin

“…While the most appropriate 3D tumor growth modeling would be using in vivo xenograft or orthotopic tumor growth in animal models, the value of assessing tumor growth using 3D in vitro modeling techniques has been recently discussed. 37,38 This is primarily performed in the context of artificial microenvironments that enforce 3D growth of cells, such as soft agarose, or more recently using more relevant basement membrane ECM extracts produced by tumor cells (e.g., matrigel). Although not without its limitations, in vitro 3D tumor cell growth does allow for more appropriate assessment of the contribution of tumor microenvironmental factors such as ECM and integrin signaling to tumor growth and invasion.…”