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Review
. 2018 Jan 18;19(1):181.
doi: 10.3390/ijms19010181.

Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions?

Jessica Hoarau-Véchot  1 , Arash Rafii  2   3 , Cyril Touboul  4   5 , Jennifer Pasquier  6   7   8
Affiliations
Review

Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions?

Jessica Hoarau-Véchot et al. Int J Mol Sci. .

Abstract

An area that has come to be of tremendous interest in tumor research in the last decade is the role of the microenvironment in the biology of neoplastic diseases. The tumor microenvironment (TME) comprises various cells that are collectively important for normal tissue homeostasis as well as tumor progression or regression. Seminal studies have demonstrated the role of the dialogue between cancer cells (at many sites) and the cellular component of the microenvironment in tumor progression, metastasis, and resistance to treatment. Using an appropriate system of microenvironment and tumor culture is the first step towards a better understanding of the complex interaction between cancer cells and their surroundings. Three-dimensional (3D) models have been widely described recently. However, while it is claimed that they can bridge the gap between in vitro and in vivo, it is sometimes hard to decipher their advantage or limitation compared to classical two-dimensional (2D) cultures, especially given the broad number of techniques used. We present here a comprehensive review of the different 3D methods developed recently, and, secondly, we discuss the pros and cons of 3D culture compared to 2D when studying interactions between cancer cells and their microenvironment.

Keywords: 2D culture; 3D anchorage independent culture; 3D culture; chemoresistance; tumor microenvironment; tumor migration; tumor proliferation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Common 3D techniques used for the creation of spheroids. (A) Hanging drop methods. Cells are deposited on a petri dish lid, which is flipped over a petri dish containing PBS; (B) ultra low attachment plates. Cells are seeded in an ultra-low attachment plate which prevents them from adhering; (C) suspension cultures. Cells are placed in spinner flasks (left) or bioreactors (right) and put under gravitational forces; (D) scaffold based-models. Cells are either seeded on the top of a hydrogel (left) or embedded in it (right); (E) magnetic levitation. Cells are magnetized in culture and attracted to a magnet located on the top.
Figure 2
Figure 2
Bioprinting and Microfluidic platforms. (A) Biopaper gel is loaded with bioink spheroids that each contain an aggregate of a few thousand cells. More layers are subsequently added and as the biopaper gel dissolves, and the bioink spheroids slowly fuse together, leaving a final bioprinted structure. (B) An example of simple microfluidics system in which cancer spheroids were embedded in micro-patterned three-dimensional matrices immediately contiguous to a microchannel. (C) Schematic represents a two-chamber chip for the culture of two different cell types as monolayers in separate chambers that are linked through a porous membrane.
Figure 3
Figure 3
Cancer and stromal cells co-culture in 2D. Schematic illustrates cell behavior at different stages (seeding, proliferative phase, and confluence) of a 2D culture model. Stromal cells (in red) and cancer cells (in blue) have the same access to the media growth factors. Cells with contact inhibition (stromal cells) slow down their division while the space availability decreases until complete stop. Cells with no contact inhibition (cancer cells) keep proliferating and start to grow on the top of other cells.
Figure 4
Figure 4
Spheroid organization Tumor spheroids are organized in three different layers with a dying core, a quiescent intermediate layer and a proliferating rim. Stromal cells (in red) are organized in a different way inside the spheroid depending of the context.
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