Three‑dimensional models to study breast cancer (Review)

Abstract

Breast cancer (BC) is the most commonly occurring cancer and primary cause of cancer-related mortality in women worldwide. Investigations into BC have been conducted in in vitro and in vivo models. Of these models, the cultivation of tumor cell lines in two-dimensional models is the most widely employed in vitro model to study tumor physiology. However, this approach does not accurately model all aspects observed in tumors. To address these limitations, three-dimensional (3D) in vitro models have been developed. In these, it is possible to reproduce the interaction between tumor cells and the extracellular matrix, as well as the interrelationship between tumor cells and stromal cells, in order to replicate the interactions observed within the 3D environment of in vivo tumors. The present review summarizes the most common 3D in vitro models used to study BC, including spheroid models, organ-on-a-chip models, hydrogel models and bio-printed models, with a discussion of their particular advantages and limitations. Contents1. Introduction 2. Spheroid models 3. Organ-on-a-chip models 4. Hydrogel models 5. Bio-printing models 6. Conclusions

Targeting cholesterol impairs cell invasion of all breast cancer types

“…3D spheroids better mimic tumor features than 2D cultures in terms of gene expression, physico-chemical gradients and cell–cell and cell-ECM interactions [ 29 ]. Moreover, growing cells in 2D offers unlimited access to nutrients, oxygen, growth factors and metabolites, contrarily to 3D spheroids in which diffusion is limited to the outer cell layers, forming a gradient with the central core [ 30 ]. Chol metabolism is also differentially regulated when switching from 2D to 3D culture as attested by the differential expression of chol biosynthesis genes and effect of chol synthesis inhibitors, like statins, on breast cancer cell growth and invasion [ 9 , 11 , 31 ].…”

Multi-omics analysis based on 3D-bioprinted models innovates therapeutic target discovery of osteosarcoma

“…Current pre-clinical cancer models, especially the widely employed 2D models, show limited efficacy in reproducing tumour complexity [ 35 , 36 ]. 3D-bioprinting is a revolutionary technology and an ideal method to replicate the meticulous structure of tissues and the interrelationship between tumour cells and the ECM.…”

Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance

“…Unlike the oversimplified 2D models, 3D models attempt to recapitulate the native tumor microenvironment in vitro by building a 3D culture environment that supports cell-cell and cell-matrix interactions. 210 , 211 Emerging evidence suggests that the DCIS-IDC transition partially results from interactions between DCIS cells and their TME, 139 , 140 , 186 and that 3D culture models provide a significant in vitro model by co-culturing tumor cells with stromal cells. 187 , 211 – 215 Carter et al developed a novel 3D culture model that could recapture DCIS using a native physiological bilayer arrangement of myoepithelial and luminal cells; this differed from the traditional use of cell lines to form spheroids.…”