Three-dimensional in vitro tissue culture models of breast cancer — a review

Abstract

Three-dimensional (3D) in vitro breast tumour models have an invaluable role in tumour biology today providing some very important insights into breast cancer. As well as increasing our understanding of homeostasis, cellular differentiation and tissue organization they provide a well defined environment for cancer research in contrast to the complex host environment of an in vivo model. With the recent availability of relevant stromal elements together with the vast array of extracellular matrix constituents available, in vivo like microenvironments can be recreated. These tissue like structures more realistically model the structural architecture and differentiated function of breast cancer than a cellular monolayer providing in vivo like responses to therapeutic agents. Three dimensional in vitro models allow the study of cell-cell and cell-extracellular matrix interactions, in addition to the influence of the microenvironment on cellular differentiation, proliferation, apoptosis and gene expression. Due to their enormous potential 3D cultures are currently being exploited by many other branches of biomedical science with therapeutically orientated studies becoming the major focus of research. In return great progress in 3D culture techniques have been made, largely due to this greater interaction. At present they are being used in studies ranging from investigating the role of adhesion molecules (e.g., E-cadherin) in invasion/metastasis; VEGF and angiogenesis, to tissue modelling and remodelling. Progress in the development of complex 3D culture systems is more productive than ever, however further research is vital.

Peripheral neural cell sensitivity to mTHPC-mediated photodynamic therapy in a 3D in vitro model

“…This used a thin collagen gel as a support substrate for the cells under investigation, enabling a powerful combination of cell death analysis and cell identification to be carried out. Collagen gels have been used as culture substrates for many years because they provide a 3D environment in which cells can grow in a more natural spatial and physical environment than they would on a stiff monolayer substrate (Kim et al, 2004;Brown and Phillips, 2007). The rate of diffusion of oxygen and other nutrients through collagen gels is relatively rapid, facilitating cell survival under normal conditions and ensuring that oxygen availability does not become a limiting factor during PDT treatment.…”

Cell viability assessment using the Alamar blue assay: A comparison of 2D and 3D cell culture models

“…For example, it is well accepted that, in an environment mirroring the in vivo conditions encountered by the cells, the observations made are more representative of the cancerous cell phenotype compared to those found on conventionally used 2D cultures (Breslin and O'Driscoll, 2012;Elliott and Yuan, 2011;Kimlin et al, 2011). Moreover, providing a microenvironment with adequate adhesion and proliferation has been reported to allow a more accurate investigation of cellular homeostasis, differentiation and migration (Kim, 2005;Kim et al, 2004). The use of collagen gels and more complex multi-component systems such as Matrigel has become increasingly popular, as they provide the cells with a matrix which more accurately represents the extra cellular matrix (ECM) (Petersen et al, 1992;Prestwich, 2008;Weaver et al, 1995).…”

Viscoelastic Imaging of Breast Tumor Microenvironment With Ultrasound

“…Recent discoveries in the molecular biology of breast cancer suggest that diagnostic specificity can be improved if we (a) directly image signaling molecules or associated receptors (molecular imaging) or (b) indirectly image the causes or effects of signaling and associated metabolic and structural responses (imaging features of the tumor microenvironment). We study mechanical properties of tissues affected by pO 2 , pH, metabolic rate, and mechanical stress since these features are environmental stimuli promoting or inhibiting signaling processes that influence tumorigenic phenotypes (3,4).…”